Aminoacyl-tRNA synthetase, class I, anticodon-binding domain, subdomain 2
Type:
Homologous_superfamily
Description:
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Structurally, an α-helix-bundle anticodon-binding domain characterises the class Ia synthetases, whereas the class Ib synthetases, GlnRS and GluRS have distinct anticodon-binding domains. The anticodon-binding domain has a multi-helical structure, consisting of two all-alpha subdomains. The Rossmann-fold, made up of alternate α-helices and β-sheets involved in ATP binding in the extended conformation, and the anticodon-binding domains are connected by a beta-α-α-beta-alpha topology ('SC fold') domain that contains the class I specific KMSKS motif [
,
].
ATP synthase inhibitor prevents the enzyme from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation [
] ATP synthase inhibitor forms a one to one complex with the F1 ATPase, possibly by binding at the α-β interface. It is thought to inhibit ATP synthesis by preventing the release of ATP []. The minimum inhibitory region for bovine inhibitor () is from residues 39 to 72 [
]. The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH , the inhibitor forms a dimer via antiparallel coiled coil interactions between the C-terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity [].
This entry represents beta-hexosaminidase (
). There are 3 forms of beta-hexosaminidase: hexosaminidase A is a trimer, with one alpha, one beta-A and one beta-B chain; hexosaminidase B is a tetramer of two beta-A and two beta-B chains; and hexosaminidase S is a homodimer of alpha chains. The two beta chains are derived from the cleavage of a precursor.
In the brain and other tissues, beta-hexosaminidase A degrades GM2 gangliosides; specifically, the enzyme hydrolyses terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. Mutations in the beta-hexosaminidase beta-chain lead to Sandhoff disease, a lysosomal storage disorder characterised by accumulation of GM2 ganglioside [
].Beta-hexosaminidase belongs to the glycoside hydrolase family 20 (
).
Eukaryotic translation initiation factor A (eIF-1A) (formerly known as eiF-4C) is a protein that seems to be required for maximal rate of protein biosynthesis. It enhances ribosome dissociation into subunits and stabilises the binding of the initiator Met-tRNA to 40S ribosomal subunits [
]. The archaea possess an eIF-1A homologue.
S14 is one of the proteins from the small ribosomal subunit.
In Escherichia coli, S14 is known to be required for the assembly of 30S particlesand may also be responsible for determining the conformation of 16S rRNA at the A site.
It belongs to a family of ribosomal proteins [] thatinclude bacterial, algal and plant chloroplast S14, yeast mitochondrial MRP2, cyanelle S14, archaebacteria Methanococcus vannielii S14, as well as yeast mitochondrial MRP2, yeast YS29A/B, and mammalian S29.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].S14 is one of the proteins from the small ribosomal subunit.
In Escherichia coli, S14 is known to be required for the assembly of 30S particlesand may also be responsible for determining the conformation of 16S rRNA at the A site.
It belongs to a family of ribosomal proteins [] thatinclude bacterial, algal and plant chloroplast S14, yeast mitochondrial MRP2, cyanelle S14, archaebacteria Methanococcus vannielii S14, as well as yeast mitochondrial MRP2, yeast YS29A/B, and mammalian S29.
The ubiquitous 2-oxoacid dehydrogenases are a family of very large multienzyme
complexes consisting of multiple copies of at least three enzymes whichcatalyze the oxidative decarboxylation of several different 2-oxoacids,
resulting in acyl-CoA products. Members of this family include pyruvatedehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2-
oxoacid dehydrogenase (BCDH). The three enzymes assembling to form thesecomplexes are the decarboxylase E1 (called E1p, E1o and E1b in PDH, OGDH and
BCDH, respectively), dihydrolipoamide acetyl, succinyl and branched-chaintransferase E2 (E2p, E2o and E2b, respectively) and dihydrolipoamide
dehydrogenase E3. The E3 component is identical in all three complexes (PDH,OGDH and BCDH) and catalyzes the same reaction. The structural core of all 2-
oxoacid dehydrogenase complexes (ODHc) is formed of multiple copies of E2subunits, with the E1 and E3 subunits bound on the periphery. The E2 component
of the ODHc's of both bacteria and eukaryotes serves as the structural core ofthese multienzyme complexes and is comprised of three types of domains.
Starting with the N terminus, there are 1-3 tandem repeated lipoyl domains(LD), followed by a peripheral subunit-binding domain (PSBD)
responsible for binding E1/E3 chains. The third domain is the C-terminalcatalytic domain (CD). The individual domains are separated by long, flexible
linker regions allowing large movements of the lipoyl domain(s) to enableactive site coupling. The PSBD domain binds E1 or E3, but not both
simultaneously. The flexible linker allows the PSBD domain (associated witheither E1 or E3) to move quite freely with respect to the core formed E2
catalytic domains [,
,
,
,
].The ~35-residue PSBD domain has a compact structure consisting of two short,
parallel α-helices (H1 and H2) separated by a loop (L1), a single helicalturn, and a further, less well-ordered loop (L2) (see PDB:1BAL). The compact
structure of the PSBD domain is stabilized mainly by hydrophobic interactions.The interactions between the PSBD domain and E3 are all mediated by charged
side chains, forming an 'electrostatic zipper'. The residues of the PSBDdomain involved in the interactions are all provided by helix H1 of this
domain. Helix H2 of PSBD does not interact with E3, but may be involved inbinding E1 [
,
,
].
This domain is found in the lipoamide acyltransferase component of the branched-chain alpha-keto acid dehydrogenase complex
, which catalyses the overall conversion of alpha-keto acids to acyl-CoA and carbon dioxide [
]. It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamideacyltransferase (E2) and lipoamide dehydrogenase (E3). The domain is also found in the dihydrolipoamide succinyltransferase component of the 2-oxoglutarate dehydrogenase complex
.
These proteins contain one to three copies of a lipoyl binding domain followed by the catalytic domain.
Methylthioribose-1-phosphate isomerase, an enzyme of the methionine salvage pathway, catalyses the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P) [
].The enzyme can be divided into two domains, the N-terminal domain and the C-terminal domain. The N-terminal domain folds into a three-stranded antiparallel β-sheet followed by five α-helices [
].
Synonym(s): CMP-N-acetylneuraminic acid synthetaseAcylneuraminate cytidylyltransferase (
) (CMP-NeuAc synthetase) catalyzes the reaction of CTP and NeuAc to form CMP-NeuAc, which is the nucleotide sugar donor used by sialyltransferases [
]. The outer membrane lipooligosaccharides of some microorganisms contain terminal sialic acid attached to N-acetyllactosamine and so this modification may be important in pathogenesis.This family also includes 8-amino-3,8-dideoxy-manno-octulosonate cytidylyltransferase found in the bacterial genus Shewanella, which is important in the development of the outer cell membrane and converts 3-deoxy-d-manno-octulosonic acid to 8-amino-3,8-dideoxy-d-manno-octulosonic acid (KDO8N) for incorporation into the lipopolysaccharide [
].
3-Deoxy-D-manno-octulosonate cytidylyltransferase (
) activates KDO, a required 8-carbon sugar, for incorporation into bacterial lipopolysaccharide in Gram-negative bacteria. It acts as a homodimer and catalyses the conversion of CTP and 3-deoxy-D-manno-octulosonate into CMP-3-deoxy-D-manno-octulosonate and pyrophosphate [
,
]. KDO is an essential component of the lipopolysaccharide found in the outer surface of Gram-negative eubacteria. It is also a constituent of the capsular polysaccharides of some Gram-negative eubacteria. Its presence in the cell wall polysaccharides of green algae and plant were also discovered. However, they have not been found in yeast and animals. The absence of the enzyme in mammalian cells makes it an attractive target molecule for drug design [].This family also includes 8-amino-3,8-dideoxy-manno-octulosonate cytidylyltransferase (
). This enzyme activates KDO8N, the 8-aminated form of KDO, for incorporation into bacterial lipopolysaccharide in the Shewanella genus. KDO8N is found exclusively in marine bacteria of the genus Shewanella [
].
Members of this family catalyse the transfer reaction of N-acetylglucosamine and N-acetylgalactosamine from the respective UDP-sugars to the non-reducing end of [glucuronic acid]beta 1-3[galactose]beta 1-O-naphthalenemethanol, an acceptor substrate analog of the natural common linker of various glycosylaminoglycans. They are also required for the biosynthesis of heparan-sulphate [
].
This group represents L-type lectins from plants, including leukoagglutinins which bind sialic acid [
].Lectins are carbohydrate-binding proteins. Leguminous lectins form one of the largest lectin families and resemble each other in their physicochemical properties, though they differ in their carbohydrate specificities. They bind either glucose/mannose or galactose [
]. Carbohydrate-binding activity depends on the simultaneous presence of both acalcium and a transition metal ion [
]. The exact function of legume lectins is not known, but they may be involved in the attachment of nitrogen-fixing bacteria to legumes and in the protection against pathogens [,
].Some legume lectins are proteolytically processed to produce two chains, beta (which corresponds to the N-terminal) and alpha (C-terminal) [
]. The lectin concanavalin A (conA) from jack bean is exceptional in that the two chains are transposed and ligated (by formation of a new peptide bond). The N terminus of mature conA thus corresponds to that of the alpha chain and the C terminus to the beta chain []. Though the legume lectins monomer is structurally well conserved, their quaternary structures vary widely [].
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Members of this family belong to the chitinase class II group which includes chitinase, chitodextrinase and the killer toxin of Kluyveromyces lactis (Yeast) (Candida sphaerica) and all belong to glycoside hydrolase, family 18
. The chitinases hydrolyse chitin oligosaccharides. However, glycoside hydrolase family 18 also includes chitinase-like proteins, which bind but do not cleave chitin [
,
].
The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([intenz:2.4.1.-]) and related proteins into distinct sequence based families has been described []. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.These enzymes belong to the glycosyltransferase family 19
. Lipid-A-disaccharide synthetase
is involved with acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase and tetraacyldisaccharide 4'-kinase
in the biosynthesis of the phosphorylated glycolipid, lipid A, in the outer membrane of Escherichia coli and other bacteria. These enzymes catalyse the first disaccharide step in the synthesis of lipid-A-disaccharide.
Glutamyl/glutaminyl-tRNA synthetase, class Ib, anti-codon binding domain
Type:
Domain
Description:
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [
].Glutamate-tRNA ligase (also known as glutamyl-tRNA synthetase;
) is a class Ic ligase and shows several similarities with glutamate-tRNA ligase concerning structure and catalytic properties. It is an alpha2 dimer. To date one crystal structure of a glutamate-tRNA ligase (Thermus thermophilus) has been solved. The molecule has the form of a bent cylinder and consists of four domains. The N-terminal half (domains 1 and 2) contains the 'Rossman fold' typical for class I ligases and resembles the corresponding part of Escherichia coli GlnRS, whereas the C-terminal half exhibits a GluRS-specific structure [
].
Glutaminyl-tRNA synthetase, class Ib, non-specific RNA-binding domain 2
Type:
Domain
Description:
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].This is a region found N-terminal to the catalytic domain of glutaminyl-tRNA synthetase (
) in eukaryotes but not in Escherichia coli. This region is thought to bind RNA in a non-specific manner, enhancing interactions between the tRNA and enzyme, but is not essential for enzyme function [
].
This entry represents the lipocalin/cytosolic fatty-acid binding domain of a group of proteins that belong to the calycin superfamily. Proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids share limited
regions of sequence homology and a common tertiary structure architecture [,
,
,
,
]. This is an eight stranded antiparallel β-barrel with a repeated + 1 topology enclosing
a internal ligand binding site [,
]. The name 'lipocalin' has been proposed [] forthis protein family, but cytosolic fatty-acid binding proteins are also included. The sequences of most members of the family, the core or kernal lipocalins, are characterised by
three short conserved stretches of residues, while others, the outlier lipocalin group, share only one or two of these[
,
]. Proteins known to belong to this family include alpha-1-microglobulin (protein HC);alpha-1-acid glycoprotein (orosomucoid) [
]; aphrodisin; apolipoprotein D; beta-lactoglobulin; complementcomponent C8 gamma chain [
]; crustacyanin []; epididymal-retinoic acid binding protein(E-RABP) [
]; insectacyanin; odorant-binding protein (OBP); human pregnancy-associated endometrial alpha-2globulin; probasin (PB), a rat prostatic protein; prostaglandin D synthase (
) [
]; purpurin; VonEbner's gland protein (VEGP) [
]; and lizard epididymal secretory protein IV (LESP IV) [].
The lipocalins are a diverse, interesting, yet poorly understood family of
proteins composed, in the main, of extracellular ligand-binding proteins displaying high specificity for small hydrophobic molecules []. Functions of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration, and the enzymatic synthesis of prostaglandins. For example, retinol-binding protein 4 transfers retinol from the stores in the liver to peripheral tissues [].The crystal structures of several lipocalins have been solved and show a
novel 8-stranded anti-parallel β-barrel fold well conserved within the family. Sequence similarity within the family is at a much lower level and would seem to be restricted to conserved disulphides and 3 motifs, which form a juxtaposed cluster that may act as a common cell surface receptor site [,
]. By contrast, at the more variable end of the fold are found an internal ligand binding site and a putative surface for the formation of macromolecular complexes []. The anti-parallel β-barrel fold is also exploited by the fatty acid-binding proteins, which function similarly by binding small hydrophobic molecules. Similarity at the sequence level, however, is less obvious, being confined to a single short N-terminal motif.This entry represents the Lipocalin conserved site. The sequences of most members of the family, the core or kernal lipocalins, are characterised by three short conserved stretches of residues [
]. Others, the outlier lipocalin group, share only one or two of these. This signature pattern was built around the first, common to all outlier and kernal lipocalins, which occurs near the start of the first β-strand.
This entry represents the APO domain which is found in plant APO (Accumulation of photosystem) proteins. The domain contains conserved cysteine and histidine residues [
]. It functions as an RNA-binding domain [].
Enolase (2-phospho-D-glycerate hydrolase) is an essential glycolytic enzyme that catalyses the interconversion of 2-phosphoglycerate and phosphoenolpyruvate [
,
]. In vertebrates, there are 3 different, tissue-specific isoenzymes, designated alpha, beta and gamma. Alpha is present in most tissues, beta is localised in muscle tissue, and gamma is found only in nervous tissue. The functional enzyme exists as a dimer of any 2 isoforms. In immature organs and in adult liver, it is usually an alpha homodimer, in adult skeletal muscle, a beta homodimer, and in adult neurons, a gamma homodimer. In developing muscle, it is usually an alpha/beta heterodimer, and in the developing nervous system, an
alpha/gamma heterodimer []. The tissue specific forms display minor kinetic differences. Tau-crystallin, one of the major lens proteins in some fish, reptiles and birds, has been shown [] to be evolutionary related to enolase.Neuron-specific enolase is released in a variety of neurological diseases, such as multiple sclerosis and after seizures or acute stroke. Several tumour cells have also been found positive for neuron-specific enolase. Beta-enolase deficiency is associated with glycogenosis type XIII defect.The signature pattern for this entry is a conserved region located in the C-terminal third of the sequence.
Enolase (2-phospho-D-glycerate hydrolase) is an essential, homodimeric enzyme that catalyses the reversible dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate as part of the glycolytic and gluconeogenesis pathways [
,
]. The reaction is facilitated by the presence of metal ions []. In vertebrates, there are 3 different, tissue-specific isoenzymes, designated alpha, beta and gamma. Alpha is present in most tissues, beta is localised in muscle tissue, and gamma is found only in nervous tissue. The functional enzyme exists as a dimer of any 2 isoforms. In immature organs and in adult liver, it is usually an alpha homodimer, in adult skeletal muscle, a beta homodimer, and in adult neurons, a gamma homodimer. In developing muscle, it is usually an alpha/beta heterodimer, and in the developing nervous system, an alpha/gamma heterodimer []. The tissue specific forms display minor kinetic differences. Tau-crystallin, one of the major lens proteins in some fish, reptiles and birds, has been shown [] to be evolutionary related to enolase.Neuron-specific enolase is released in a variety of neurological diseases, such as multiple sclerosis and after seizures or acute stroke. Several tumour cells have also been found positive for neuron-specific enolase. Beta-enolase deficiency is associated with glycogenosis type XIII defect.
This family includes the GTP-binding protein BipA or TypA (Tyrosine phosphorylated protein A (TypA), also known as 50S ribosomal subunit assembly factor BipA) from bacteria and its homologue from Arabidopsis (putative elongation factor TypA-like SVR3). BipA is a 50S ribosomal subunit assembly protein with GTPase activity, required for 50S subunit assembly at low temperatures, also functions as a translation factor that is required specifically for the expression of the transcriptional modulator Fis. BipA binds the 70S ribosome at a site that coincides with that of EF-G and has a GTPase activity that is sensitive to high GDP:GTP ratios and is stimulated by 70S ribosomes programmed with mRNA and aminoacylated tRNAs [
,
]. The growth rate-dependent induction of BipA allows the efficient expression of Fis, thereby modulating a range of downstream processes, including DNA metabolism and type III secretion. This GTPase impacts interactions between enteropathogenic E.coli (EPEC) and epithelial cells and also has an effect on motility []. It appears to be involved in the regulation of several processes important for infection, including rearrangements of the cytoskeleton of the host, bacterial resistance to host defence peptides, flagellum-mediated cell motility, and expression of K5 capsular genes [,
].TypA-like SVR3 is a putative chloroplastic elongation factor involved in response to chilling stress. It is required for proper chloroplast rRNA processing and/or translation at low temperature [] and it is also involved in plastid protein homeostasis [].
In budding yeasts, Mak16 forms part of the 66S pre-ribosomal particles and functions as a transacting actor involved in rRNA processing [
,
]. The Schistosoma mansoni (Blood fluke) Mak16 has been shown to target protein transport to the nucleolus [].
OPA3 deficiency causes type III 3-methylglutaconic aciduria (MGA) in humans. This disease manifests with early bilateral optic atrophy, spasticity, extrapyramidal dysfunction, ataxia, and cognitive deficits, but normal longevity [
].This family consists of several optic atrophy 3 (OPA3) proteins and related proteins from other eukaryotic species, the function is unknown.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This family consists of ribosomal protein L5 from eukaryotes. The ribosomal 5S RNA is the only known rRNA species to bind a ribosomal protein before its assembly into the ribosomal subunits [
]. In eukaryotes, the 5S rRNA molecule binds one protein species, a 34kDa protein which has been implicated in the intracellular transport of 5 S rRNA [
]. This family also includes ribosomal proteins L18 from archaea.
Photosystem II cytochrome b559, alpha subunit, lumenal region
Type:
Domain
Description:
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. The alpha subunit (PsbE) of cytochrome b559, forms a haem-binding heterodimer with the beta subunit (PsbF) (
) within the reaction centre core of PSII. Both PsbE and PsbF are essential components for PSII assembly, and are probably involved in secondary electron transport mechanisms that help to protect PSII from photo-damage [
].This domain occurs in the lumenal region of the alpha subunit. It is usually found in conjuction with an N-terminal domain (
).
The cro/C1-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 residues present in transcriptional regulators. The domain is named after the transcriptional repressors cro and C1 of temperate bacteriophages 434 and lambda, respectively. Besides in bacteriophages, cro/C1-type regulators are present in prokaryotes and in eukaryotes. The helix-turn-helix DNA-binding motif is generally located in the N-terminal part of these transcriptional regulators. The C-terminal part may contain an oligomerization domain, e.g. C1 repressors and CopR act as dimers, while SinR is a tetramer. The cro/C1-type HTH domain also occurs in combination with the TPR repeat and the C-terminal part of C-5 cytosine-specific DNA methylases contains regions related to the enzymatic function.Several structures of cro/C1-type transcriptional repressors have been resolved and their DNA-binding domain encompasses five α-helices, of which the extremities are less conserved [
]. The helix-turn-helix motif comprises the second and third helices, the third being called the recognition helix. The HTH is involved in DNA-binding into the major groove, where the recognition helix makes most DNA-contacts. The bacteriophage repressors regulate lysogeny/lytic growth by binding with differential affinity to the operators. These operators show 2-fold symmetry and the repressors bind as dimers. Binding of the repressor to the operator positions the DNA backbone into a slightly bent twist [,
].
This domain is found in the multiprotein bridging factor 1 (MBF1) which forms a heterodimer with MBF2. It has been shown to make direct contact with the TATA-box binding protein (TBP) and interacts with Ftz-F1, stabilising the Ftz-F1-DNA complex [
]. It is also found in the endothelial differentiation-related factor (EDF-1). Human EDF-1 is involved in the repression of endothelial differentiation, interacts with CaM and is phosphorylated by PKC []. The domain is found in a wide range of eukaryotic proteins including metazoans, fungi and plants. A helix-turn-helix motif () is found to its C terminus.
Bacteriophage lambda C1 repressor controls the expression of viral genes as part of the lysogeny/lytic growth switch. C1 is essential for maintaining lysogeny, where the phage replicates non-disruptively along with the host. If the host cell is threatened, then lytic growth is induced. The Lambda C1 repressor consists of two domains connected by a linker: an N-terminal DNA-binding domain that also mediates interactions with RNA polymerase, and a C-terminal dimerisation domain [
]. The DNA-binding domain consists of four helices in a closed folded leaf motif. Several different phage repressors from different helix-turn-helix families contain DNA-binding domains that adopt a similar topology. These include the Lambda Cro repressor, Bacteriophage 434 C1 and Cro repressors, P22 C2 repressor, and Bacteriophage Mu Ner protein.The DNA-binding domain of Bacillus subtilis spore inhibition repressor SinR is identical to that of phage repressors [
]. SinR represses sporulation, which only occurs in response to adverse conditions. This provides a possible evolutionary link between the two adaptive responses of bacterial sporulation and prophage induction.Other DNA-binding domains also display similar structural folds to that of Lambda C1. These include bacterial regulators such as the purine repressor (PurR), the lactose repressor (Lacr) and the fructose repressor (FruR), each of which has an N-terminal DNA-binding domain that exhibits a fold similar to that of lambda C1, except that they lack the first helix [
,
,
]. POU-specific domains found in transcription factors such as in Oct-1, Pit-1 and Hepatocyte nuclear factor 1a (LFB1/HNF1) display four-helical fold DNA-binding domains similar to that of Lambda C1 [,
,
]. The N-terminal domain of cyanase has an α-helix bundle motif similar to Lambda C1, but it probably does not bind DNA. Cyanase is an enzyme found in bacteria and plants that catalyses the reaction of cyanate with bicarbonate to produce ammonia and carbon dioxide in response to extracellular cyanate [].
A number of eukaryotic and archaebacterial ribosomal proteins can be grouped
on the basis of sequence similarities. One of these families consists of:Mammalian S28 [
].Plant S28 [
].Fungi S33 [
].Archaebacterial S28e.These proteins have from 64 to 78 amino acids. This entry represents a highly conserved nonapeptide from the C-terminal extremity of these proteins.NOTE: This entry matches
, which is a translation initiation factor IF-2. This is a false positive.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities. Examples are:
Mammalian S28 [
]
Plant S28 [
]
Fungi S33 [
]
Archaebacterial S28e.These proteins have from 64 to 78 amino acids and a highly conserved C-terminal region.S1-like RNA-binding domains are found in a wide variety of RNA-associated proteins. S28E protein is a component of the 30S ribosomal subunit. S28E is highly conserved among archaea and eukaryotes. S28E may control precursor RNA splicing and turnover in mRNA maturation process but its function in the ribosome is largely unknown. The structure contains an OB-fold found in many oligosaccharide and nucleic acid binding proteins. This implies that S28E might be involved in protein synthesis [
,
,
].
Proteins in this entry consist exclusively of the CCT gamma chain from animals, plants, fungi, and other eukaryotes.Members of this eukaryotic family are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1 or Tailless Complex Polypeptide 1) or TRiC [
,
]. Chaperonins are involved in productive folding of proteins []. They share a common general morphology, a double toroid of 2 stacked rings. The archaeal equivalent group II chaperonin is often called the thermosome []. Both the thermosome and the TCP-1 family of proteins are weakly, but significantly [], related to the cpn60/groEL chaperonin family (see ).
The TCP-1 protein was first identified in mice where it is especially abundant in testis but present in all cell types. It has since been found and characterised in many other animal species, as well as in yeast, plants and protists. The TCP1 complex has a double-ring structure with central cavities where protein folding takes place [
]. TCP-1 is a highly conserved protein of about 60kDa (556 to 560 residues) which participates in a hetero-oligomeric 900kDa double-torus shaped particle [] with 6 to 8 other different, but homologous, subunits []. These subunits, the chaperonin containing TCP-1 (CCT) subunit beta, gamma, delta, epsilon, zeta and eta are evolutionary related to TCP-1 itself [,
]. Non-native proteins are sequestered inside the central cavity and folding is promoted by using energy derived from ATP hydrolysis [,
,
]. The CCT is known to act as a molecular chaperone for tubulin, actin and probably some other proteins [,
].
This domain is found to the N terminus of MOSC domain (
). The function of this domain is unknown, however it is predicted to adopt a beta barrel fold.
Phenylalanyl-tRNA synthetase, class IIc, beta subunit, archaeal/eukaryotic type
Type:
Family
Description:
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Phenylalanyl-tRNA synthetase (
) is an alpha2/beta2 tetramer composed of 2 subunits that belongs to class IIc. In eubacteria, a small subunit (pheS gene) can be designated as beta (E. coli) or alpha subunit (see
). Reciprocally the large subunit
(pheT gene) can be designated as alpha (E. coli) or beta. In all other kingdoms the two subunits have equivalent length in eukaryota, and can be identified by specific signatures. The enzyme from Thermus thermophilus has an alpha 2 beta 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of phenylalanyl-tRNA synthetase as a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other synthetases [].This family describes the beta subunit. The beta subunits break into two subfamilies that are considerably different in sequence, length, and pattern of gaps (see also
). This family represents the subfamily that includes the beta subunit from eukaryotic cytosol, the archaea, and spirochetes.
Domain B5 is found in phenylalanine-tRNA synthetase beta subunits. This domain has been shown to bind DNA through a winged helix-turn-helix motif [
]. Phenylalanine-tRNA synthetase may influence common cellular processes via DNA binding, in addition to its aminoacylation function.
Kinetochores are the chromosomal sites for spindle interaction and play a vital role for chromosome segregation. Fission Saccharomyces cerevisiae kinetochore protein Mis12, is required for correct spindle morphogenesis, determining metaphase spindle length [
]. Thirty-five to sixty percent extension of metaphase spindle length takes place in Mis12 mutants []. It has been shown that Mis12 might genetically interact with Mal2p [].
This entry represents a dimerisation domain that is usually found at the C-terminal of both class I and class II oxidoreductases, as well as in NADH oxidases and peroxidases [
,
,
].
This superfamily represents a dimerisation domain that is usually found at the C-terminal of FAD and NAD-linked reductases. This domain has a core alpha+beta sandwich structure consisting of beta(3,4)-alpha(3). The first two domains are of the same beta/beta/alpha fold. This domain can be found in the following proteins:Glutathione reductase [
].Trypanothione reductase [
].Mammalian thioredoxin reductase [
].Apoptosis-inducing factor (AIF), which contains a large loop insertion in this domain [
].NADH peroxidase [
].Biphenyl 2,3-dioxygenase, ferredoxin reductase (also known as NADH-dependent ferredoxin reductase, BphA4) [
].Putidaredoxin reductase [
].Dihydrolipoyl dehydrogenase (also known as dihydrolipoamide dehydrogenase) [
].2-oxopropyl-CoM reductase, carboxylating (also known as NADH-dependent 2-ketopropyl coenzyme M oxidoreductase/carboxylase) [
].The flavin-binding subunit of flavocytochrome c sulphide dehydrogenase (FCSD) [
].NADH oxidase /nitrite reductase.
4,5-DOPA dioxygenase catalyzes the incorporation of both atoms of molecular oxygen into 4,5-dihydroxy-phenylalanine (4,5-DOPA). The reaction results in the opening of the cyclic ring between carbons 4 and 5 and producing an unstable seco-DOPA that rearranges to betalamic acid. 4,5-DOPA dioxygenase is a key enzyme in the biosynthetic pathway of the plant pigment betalain [
,
]. Homologues of DODA are present not only in betalain-producing plants, but also in bacteria and archaea []. This enzyme is a member of the class III extradiol dioxygenase family, a group of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon.
Extradiol ring-cleavage dioxygenase, class III enzyme, subunit B
Type:
Domain
Description:
Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of aromatic compounds. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes (
) use a non-haem Fe(III) to cleave the aromatic ring between two hydroxyl groups (ortho-cleavage), whereas extradiol enzymes use a non-haem Fe(II) to cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon (meta-cleavage) [
,
]. These two subfamilies differ in sequence, structural fold, iron ligands, and the orientation of second sphere active site amino acid residues. Extradiol dioxygenases are usually homo-multimeric, bind one atom of ferrous ion per subunit and have a subunit size of about 33kDa. Extradiol dioxygenases can be divided into three classes. Class I and II enzymes () show sequence similarity, with the two-domain class II enzymes having evolved from a class I enzyme through gene duplication. Class III enzymes are different in sequence and structure, but they do share several common active-site characteristics with the class II enzymes, in particular the coordination sphere and the disposition of the putative catalytic base are very similar.
Class III enzymes usually have two subunits, designated A and B. Enzymes that belong to the extradiol class III family include Protocatechuate 4,5-dioxygenase (4,5-PCD; LigAB) (
) [
]; and 2'-aminobiphenyl-2,3-diol 1,2-dioxygenase (CarBaBb) [].The crystal structure of dioxygenase LigAB revealed that the molecule is an alpha2beta2 tetramer. The active site contains a non-heme iron coordinated by His12, His61, Glu242, and a water molecule located in a deep cleft of the beta subunit, which is covered by the alpha subunit [
].This entry represents the structural domain of subunit B.
Rxt3 is a component of the Rpd3L histone deacetylase complex that is responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) [
].
The LCCL domain has been named after the best characterised proteins that were found to contain it, namely Limulus factor C, Coch-5b2 and Lgl1. It is an about 100 amino acids domain whose C-terminal part contains a highly conserved histidine in a conserved motif YxxxSxxCxAAVHxGVI. The LCCL module is thought to be an autonomously folding domain that has been used for the construction of various modular proteins through exon-shuffling. It has been found in various metazoan proteins in association with complement B-type domains, C-type lectin domains, von Willebrand type A domains, CUB domains, discoidin lectin domains or CAP domains. It has been proposed that the LCCL domain could be involved in lipopolysaccharide (LPS) binding [
,
]. Secondary structure prediction suggests that the LCCL domain contains six beta strands and two alpha helices []. The structure of the LCCL domain from human Coch-5b2 has been solved. It has an unusual fold, where a centrally located helix is wrapped by extended polypeptide segments of mostly irregular secondary structure []. Some proteins known to contain a LCCL domain include Limulus factor C, a LPS endotoxin-sensitive trypsin type serine protease which serves to protect the organism from bacterial infection; vertebrate cochlear protein cochlin or coch-5b2 (Cochlin is probably a secreted protein, mutations affecting the LCCL domain of coch-5b2 cause the deafness disorder DFNA9 in humans); and mammalian late gestation lung protein Lgl1, contains two tandem copies of the LCCL domain [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This family includes chloroplast ribosomal protein S5 as well as bacterial ribosomal protein S5. A candidate mitochondrial form (Saccharomyces cerevisiae YBR251W and its homologues) differs substantially and is not included in this model.
Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [
]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence []. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [].Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [
]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [,
].This group of serine peptidases belong to MEROPS peptidase family S49 (protease IV family, clan S-). The predicted active site serine for members of this family occurs in a transmembrane domain. The domain defines sequences in viruses, archaea, bacteria and plants. These sequences are variously annotated in the different taxonomic groups, examples are:Viruses: capsid proteinArchaea: proteinase IV homologueBacteria: proteinase IV, sohB, SppA, pfaP, putative proteasePlants: SppA, protease IVThis group also contains proteins classified as non-peptidase homologues that either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity of peptidases. Related proteins, non-peptidase homologues and unclassified S49 members are also to be found in
.
Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [
]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence []. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [].Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [
]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [,
].This group of serine peptidases belong to MEROPS peptidase family S49 (protease IV family, clan S-). The predicted active site serine for members of this family occurs in a transmembrane domain.Signal peptides of secretory proteins seem to serve at least two important biological functions. First, they are required for
protein targeting to and translocation across membranes, such as the eubacterial plasma membrane and the endoplasmicreticular membrane of eukaryotes. Second, in addition to their role as determinants for protein
targeting and translocation, certain signal peptides have a signalling function.During or shortly after pre-protein translocation, the signal peptide is removed by signal peptidases. The integral membrane protein, SppA (protease IV), of Escherichia coli was shown experimentally to degrade signal peptides. The member of this family from Bacillus subtilis has only been shown to be required for efficient processing of
pre-proteins under conditions of hyper-secretion []. These enzymes have a molecular mass around 67kDa and a duplication such that the N-terminal half shares extensive homology with the C-terminal half and was shown in E. coli to form homotetramers. E. coli SohB, which is most closely homologous to the C-terminal duplication of SppA, is predicted to perform a similar function of small peptide degradation, but in the periplasm.Many prokaryotes have a single SppA/SohB homologue that may perform the function of either or both.
Ribosomal protein S3 is one of the proteins from the small ribosomal subunit. This family describes ribosomal protein S3 of the eukaryotic cytosol and of the archaea.Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].
This domain, Associated With SET (AWS), whose specific function is still unknown, is found in a group of histone-lysine N-methyltransferases and similar eukaryotic proteins, including Histone-lysine N-methyltransferase, H3 lysine-36 specific from humans (H3-K36-HMTase or Nsd1). Nsd1 is a transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. Mutations in this protein are associated with several human disorders such as Sotos syndrome [
,
]. This cysteine-rich domain is often found in association with the SET domain ().
ASHR3 protein, a member of this family, interacts with the putative basic helix-loop-helix transcription factor ABORTED MICROSPORES (AMS), which is involved in anther and stamen development in Arabidopsis. This interaction is mediated by the PHD finger and the SET domain of ASHR3 [
].Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [,
,
]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM []. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [,
,
]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [,
,
]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Ketol-acid reductoisomerase (KARI; (
)), also known as acetohydroxy
acid isomeroreductase (AHIR or AHAIR), catalyzes the conversion ofacetohydroxy acids into dihydroxy valerates in the second step of thebiosynthetic pathway for the essential branched-chain amino acids valine,
leucine, and isoleucine. KARI catalyzes an unusual two-step reactionconsisting of an alkyl migration in which the substrate, either 2-acetolactate
(AL) or 2-aceto-2-hydroxybutarate (AHB), is converted to 3-hydoxy-3-methyl-2-oxobutyrate or 3-hydoxy-3-methyl-2-pentatonate, followed by a NADPH-dependent
reduction to give 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylvalerate respectively [
,
,
,
,
,
].KARI is present only in bacteria, fungi, and plants, but not in animals. KARIs
are divided into two classes on the basis of sequence length andoligomerization state. Class I KARIs are ~340 amino acid residues in length
and include all fungal KARIs, whereas class II KARIs are ~490 residues longand include all plant KARIs. Bacterial KARIs can be either class I or class
II. KARIs are composed of two types of domains, an N-terminal Rossmann folddomain and one or two C-terminal knotted domains. Two intertwinned knotted
domains are required for function, and in the short-chain or class I KARIs,each polypeptide chain has one knotted domain. As a result, dimerization of
two monomers forms two complete KARI active sites. In the long-chain or classII KARIs, a duplication of the knotted domain has occurred and, as a result,
the protein does not require dimerization to complete its active site[
,
,
,
,
,
].The α-helical KARI C-terminal knotted domain can be described as a six-
helix core in which helices coil like cable threads around each other, thusforming a bundle [
,
,
,
,
].
Ketol-acid reductoisomerase (KARI; (
)), also known as acetohydroxy
acid isomeroreductase (AHIR or AHAIR), catalyzes the conversion ofacetohydroxy acids into dihydroxy valerates in the second step of the
biosynthetic pathway for the essential branched-chain amino acids valine,leucine, and isoleucine. KARI catalyzes an unusual two-step reaction
consisting of an alkyl migration in which the substrate, either 2-acetolactate(AL) or 2-aceto-2-hydroxybutarate (AHB), is converted to 3-hydoxy-3-methyl-2-
oxobutyrate or 3-hydoxy-3-methyl-2-pentatonate, followed by a NADPH-dependentreduction to give 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-
methylvalerate respectively [,
,
,
,
,
].KARI is present only in bacteria, fungi, and plants, but not in animals. KARIs
are divided into two classes on the basis of sequence length andoligomerization state. Class I KARIs are ~340 amino acid residues in length
and include all fungal KARIs, whereas class II KARIs are ~490 residues longand include all plant KARIs. Bacterial KARIs can be either class I or class
II. KARIs are composed of two types of domains, an N-terminal Rossmann folddomain and one or two C-terminal knotted domains. Two intertwinned knotteddomains are required for function, and in the short-chain or class I KARIs,
each polypeptide chain has one knotted domain. As a result, dimerization oftwo monomers forms two complete KARI active sites. In the long-chain or class
II KARIs, a duplication of the knotted domain has occurred and, as a result,the protein does not require dimerization to complete its active site
[,
,
,
,
,
].The alpha/beta KARI N-terminal Rossmann fold domain consists of a nine-stranded mixed β-sheet with flanking α-helices on both sides of the β-sheet.
Ketol-acid reductoisomerase (KARI) or acetohydroxy acid isomeroreductase catalyses the conversion of acetohydroxy acids into dihydroxy valerates. This reaction is the second in the synthetic pathway of the essential branched side chain amino acids valine and isoleucine [
]. The enzyme forms a tetramer of similar but non-identical chains, and requires magnesium as a cofactor. Most ketol-acid reductoisomerases prefer the NADPH cofactor to NADH, but NADH-utilizing enzymes has also been identified [].
Nmd3 acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit [
,
]. This N-terminal region contains four conserved CXXC motifs that could be metal binding.
This entry includes Probable splicing factor YJU2B (also known as CCDC130) and Splicing factor YJU2 (also known as CCDC94) from humans, Saf4 from fission yeasts and Yju2 from budding yeasts. Saf4 (also known as cwc16) is involved in mRNA splicing where it associates with cdc5 and the other cwf proteins as part of the spliceosome [
]. Yju2 is a splicing factor that is associated with the Prp19-associated complex and acts after Prp2 in promoting the first catalytic reaction of pre-mRNA splicing. It may play a role in stabilizing the structure of the spliceosome catalytic core [,
].
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 27
comprises enzymes with several known activities; alpha-galactosidase (
); alpha-N-acetylgalactosaminidase (
); isomalto-dextranase (
).
Alpha-galactosidase (melibiase) catalyses the hydrolysis of melibiose into
galactose and glucose []. In man, deficiency in the enzyme results inFabry's disease (X-linked sphingolipidosis). Alpha-N-acetylgalactosaminidase
catalyses the hydrolysis of terminal non-reducing N-acetyl-D-galactosamineresidues in N-acetyl-alpha-D-galactosaminides [
]. Two conserved Asp residues may be involved in the catalytic mechanism in these enzymes. Deficiency in this enzyme results in Schindler and Kanzaki diseases.
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. Families 27 () and 36 (
) encompasses alpha-galactosidases and alpha-N-acetylgalactosaminidases.Alpha-galactosidase (
) (melibiase) [
] catalyses the hydrolysis of melibiose into galactose and glucose. In man, the deficiency of this enzyme is the cause of Fabry's disease (X-linked sphingolipidosis). Alpha-galactosidase is present in a variety of organisms. There is a considerable degree of similarity in the sequence of alpha-galactosidase from various eukaryotic species. Escherichia coli alpha-galactosidase (gene melA), which requires NAD and magnesium as cofactors, is not structurally related to the eukaryotic enzymes; by contrast, an Escherichia coli plasmid encoded alpha-galactosidase (gene rafA) [] contains a region of about 50 amino acids which is similar to a domain of the eukaryotic alpha-galactosidases.Alpha-N-acetylgalactosaminidase (
) [
] catalyses the hydrolysis of terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides. In man, the deficiency of this enzyme is the cause of Schindler and Kanzaki diseases. The sequence of this enzyme is highly related to that of the eukaryotic alpha-galactosidases.This entry represents a conserved site in families 27 and 36. It contains two conserved aspartic acid residues which could be involved in the catalytic mechanism.
This domain is found in TauD/TfdA taurine catabolism dioxygenases. The Escherichia coli tauD gene is required for the utilisation of taurine (2-aminoethanesulphonic acid) as a sulphur source and is expressed only under conditions of sulphate starvation. TauD is an alpha-ketoglutarate-dependent dioxygenase catalysing the oxygenolytic release of sulphite from taurine [
]. The 2,4-dichlorophenoxyacetic acid/alpha-ketoglutarate dioxygenase from Burkholderia sp. (strain RASC) also belongs to this family []. TfdA from Ralstonia eutropha (Alcaligenes eutrophus) is a 2,4-D monooxygenase [].This domain is also found in gamma-butyrobetaine hydroxylase (GBBH), the enzyme responsible for the biosynthesis of L-carnitine, a key molecule of fatty acid metabolism. The GBBH monomer consists of this catalytic double-stranded β-helix (DBSH) domain, which is found in all 2-ketoglutarate (2KG) oxygenases, and a smaller N-terminal domain [
].
This is entry represents a domain found in mitochondrial distribution and morphology proteins Mdm12 and Mdm34, and in maintenance of mitochondrial morphology protein Mmm1. These proteins are components of the ERMES/MDM complex, which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria [
]. MMM1 is an integral ER protein conserved from plants to humans. It is N-glycosylated, and forms a complex with Mdm10, Mdm12and Mdm34 to tether the mitochondria to the endoplasmic reticulum [
].
Phosphoenolpyruvate carboxylase (PEPcase) catalyzes the irreversible β-carboxylation of phosphoenolpyruvate by bicarbonate to yield oxaloacetate and phosphate. The enzyme is found in all plants and in a variety of microorganisms. A histidine [
] and a lysine [] have been implicated in the catalytic mechanism of this enzyme; the regions around these active site residues are highly conserved in PEPcase from various plants, bacteria and cyanobacteria.This entry represents a conserved region containing the lysine active site.
Phosphoenolpyruvate carboxylase (PEPCase), an enzyme found in all multicellular plants, catalyses the formation of oxaloacetate from phosphoenolpyruvate (PEP) and a hydrocarbonate ion [
]. This reaction is harnessedby C4 plants to capture and concentrate carbon dioxide into the photosynthetic bundle sheath cells. It also plays a key role in the nitrogen
fixation pathway in legume root nodules: here it functions in concert withglutamine, glutamate and asparagine synthetases and aspartate amido transferase, to synthesise aspartate and asparagine, the major nitrogen transport compounds in various amine-transporting plant species [
]. PEPCase
also plays an antipleurotic role in bacteria and plant cells, supplyingoxaloacetate to the TCA cycle, which requires continuous input of C4
molecules in order to replenish the intermediates removed for amino acidbiosynthesis [
].The C terminus of the enzyme contains the active site that includes a
conserved lysine residue, involved in substrate binding, and other conservedresidues important for the catalytic mechanism [
].Based on sequence similarity, PEPCase enzymes can be grouped into two distinct families, one found primarily in bacteria and plants, and another found primarily in archaea.This entry represents the family found primarily in bacteria and plants.
Phosphoenolpyruvate carboxylase (PEPCase), an enzyme found in all multicellular plants, catalyses the formation of oxaloacetate from phosphoenolpyruvate (PEP) and a hydrocarbonate ion [
]. This reaction is harnessedby C4 plants to capture and concentrate carbon dioxide into the photosynthetic bundle sheath cells. It also plays a key role in the nitrogen
fixation pathway in legume root nodules: here it functions in concert withglutamine, glutamate and asparagine synthetases and aspartate amido transferase, to synthesise aspartate and asparagine, the major nitrogen transport compounds in various amine-transporting plant species [
]. PEPCase
also plays an antipleurotic role in bacteria and plant cells, supplyingoxaloacetate to the TCA cycle, which requires continuous input of C4
molecules in order to replenish the intermediates removed for amino acidbiosynthesis [
].The C terminus of the enzyme contains the active site that includes a
conserved lysine residue, involved in substrate binding, and other conservedresidues important for the catalytic mechanism [
].Based on sequence similarity, PEPCase enzymes can be grouped into two distinct families, one found primarily in bacteria and plants, and another found primarily in archaea.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].A number of eukaryotic ribosomal proteins can be grouped on the basis of
sequence similarities. These proteins have 82 to 87 amino acids. The amino termini are all N alpha-acetylated. The N-terminal halves of the protein molecules are highly conserved in contrast to the carboxy-terminal parts [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].A number of eukaryotic ribosomal proteins can be grouped on the basis of
sequence similarities. These proteins have 82 to 87 amino acids. The amino termini are all N alpha-acetylated. The N-terminal halves of the protein molecules are highly conserved in contrast to the carboxy-terminal parts [].
This domain is found in the N-terminal region of CLIP-associated proteins (CLASPs), which are widely conserved microtubule plus-end-tracking proteins that regulate the stability of dynamic microtubules [
,
]. The domain is also found in other proteins involved in microtubule binding, including STU1, MOR1 and spindle pole body component Alp14.
Translationally controlled tumour protein, conserved site
Type:
Conserved_site
Description:
The translationally controlled tumor proteins (TCTPs, such as p21, p23 and
histamine releasing factor (HRF)) are a highly conserved and abundantlyexpressed family of eukaryotic proteins that are implicated in a variety of
cellular functions, including microtubule stabilization, cell cycle,apoptosis, and cytokine release. TCTP is ubiquitously expressed in all
eukaryotic organisms from protozoa such as Plasmodium sp. to plants andmammals [
,
,
,
].This entry represents two conserved sites in these proteins.
This superfamily represents a structural domain with a complex fold consisting of several coiled β-sheets. This domain exists as a duplication, consisting of a tandem repeat of two similar structural motifs. This entry represents copies of this structural motif in the following protein families:Mss4, which contains a zinc-binding site.Translationally controlled tumour-associated protein TCTP, which contains an insertion of an α-helix hairpin, and which lacks a zinc-binding site.Mss4 is a conserved accessory factor for Rab GTPases, which function as ubiquitous regulators of intracellular membrane trafficking [
]. Mss4 acts to promote nucleotide release from exocytic but not endocytic Rab GTPases. Mss4 has a complex fold made of several coiled β-sheets, and consists of a duplication of tandem repeats of two similar structural motifs. It contains a zinc-binding site.Other proteins that show structural similarity to Mss4 include the translationally controlled tumour-associated proteins TCTPs, which contain an insertion of an alpha helical hairpin, and lack the zinc-binding site. TCTPs are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and the human acute allergic response [
].
Mammalian translationally controlled tumour protein (TCTP) (or P23) is a protein which has been found to be preferentially synthesised in cells during the early growth phase of some types of tumour [
,
], but which is also expressed in normal cells. The physiological function of TCTP is still not known. It was first identified as a histamine-releasing factor, acting in IgE +-dependent allergic reactions. In addition, TCTP has been shown to bind to tubulin in the cytoskeleton, has a high affinity for calcium, is the binding target for the antimalarial compound artemisinin, and is induced in vitamin D-dependent apoptosis. TCTP production is thought to be controlled at the translational as well as the transcriptional level []. TCTP is a hydrophilic protein of 18 to 20 kD. TCTPs do not share significant sequence similarity with any other class of proteins. Recently, the structure of TCTP was determined and exhibited significant structural similarity to the human protein Mss4, which is a guanine nucleotide-free chaperone of the Rab protein [
]. Close homologues have been found in plants [], earthworm [], Caenorhabditis elegans (F52H2.11), Hydra, Saccharomyces cerevisiae (YKL056c) [] and Schizosaccharomyces pombe (SpAC1F12.02c).
This entry includes condensin subunit 1 (CND1) and condensin-2 complex subunit D3 (NCAPD3).CND1 is a regulatory subunit of the condensin complex (contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: NCAPH/BRRN1, NCAPD2/CAPD2 and NCAPG), a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes [
]. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases [,
,
,
]. NCAPD3 is a regulatory subunit of the condensin-2 complex (contains the SMC2 and SMC4 heterodimer, and 3 non SMC subunits that probably regulate the complex: NCAPH2, NCAPD3 and NCAPG2), a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis [
].
Adenosine deaminase (
) catalyzes the hydrolytic deamination of adenosine into
inosine and AMP deaminase () catalyzes the hydrolytic deamination of AMP into IMP.
It has been shown [] that these two enzymes share three regions of sequence similarities; these regions are centred
on residues which are proposed to play an important role in the catalytic mechanism of these two enzymes. This entry presents one of these
regions, it contains two conserved aspartic acid residues that are potentialactive site residues.
Protein families that contain at least one copy of this domain include citrate lyase ligase, pantoate-beta-alanine ligase, glycerol-3-phosphate cytidyltransferase [
], ADP-heptose synthase, phosphocholine cytidylyltransferase, lipopolysaccharide core biosynthesis protein KdtB, the bifunctional protein NadR, archaeal FAD synthase RibL [], and a number whose function is unknown. Many of these proteins are known to use CTP or ATP and release pyrophosphate.
This family represents a conserved region within a number of proteins of unknown function that seem to be specific to Arabidopsis thaliana. Note that some family members contain more than one copy of this region.
The formiminotransferase (FT) domain of formiminotransferase-cyclodeaminase (FTCD) forms a homodimer, with each protomer being comprised of two subdomains. The formiminotransferase domain has an N-terminal subdomain that is made up of a six-stranded mixed β-pleated sheet and five alpha helices, which are arranged on the external surface of the beta sheet. This, in turn, faces the β-sheet of the C-terminal subdomain to form a double β-sheet layer. The two subdomains are separated by a short linker sequence, which is not thought to be any more flexible than the remainder of the molecule. The substrate is predicted to form a number of contacts with residues found in both the N-terminal and C-terminal subdomains [
].This entry represents the N-terminal subdomain of the formiminotransferase domain.
This entry represents the formiminotransferase (FT) domain of formiminotransferase-cyclodeaminase (FTCD), which forms a homodimer, with each protomer being comprised of two subdomains. Each subdomain has the structure consisting of an alpha/beta sandwich with antiparallel β-sheet in the form (beta-α-β)x2. Tetrahydrofolate (THF)-dependent glutamate formiminotransferase is involved in the histidine utilization pathway. This enzyme interconverts L-glutamate and N-formimino-L-glutamate. The enzyme is bifunctional as it also catalyzes the cyclodeaminase reaction on N-formimino-THF, converting it to 5,10-methenyl-THF and releasing ammonia; part of the process of regenerating THF. This model covers enzymes from metazoa as well as Gram-positive bacteria and archaea. In humans, deficiency of this enzyme results in a disease phenotype [
]. The crystal structure of the enzyme has been studied in the context of the catalytic mechanism [].This superfamily represents both individual subdomains of the formiminotransferase catalytic domain.
The formiminotransferase (FT) domain of formiminotransferase-cyclodeaminase (FTCD) forms a homodimer, with each protomer being comprised of two subdomains. The formiminotransferase domain has an N-terminal subdomain that is made up of a six-stranded mixed β-pleated sheet and five alpha helices, which are arranged on the external surface of the beta sheet. This, in turn, faces the β-sheet of the C-terminal subdomain to form a double β-sheet layer. The two subdomains are separated by a short linker sequence, which is not thought to be any more flexible than the remainder of the molecule. The substrate is predicted to form a number of contacts with residues found in both the N-terminal and C-terminal subdomains []. In humans, deficiency of this enzyme results in a disease phenotype [].This entry represents the C-terminal subdomain of the formiminotransferase domain.
The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded by ORC1-6 [
]. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle []. ORC directs DNA replication throughout the genome and is required for its initiation [,
,
]. ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex [,
,
,
]. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase [,
,
]. Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase [,
,
,
]. In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) [
,
,
]. ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers [,
,
]. Both ORC1 and ORC5 bind ATP, although only ORC1 has ATPase activity [
]. ORC1 and ORC4 constitute the primary DNA binding site in the ORC ring []. The binding of ATP by ORC1 is required for ORC binding to DNA and is essential for cell viability []. The ATPase activity of ORC1 is involved in formation of the pre-RC [,
,
]. ATP binding by ORC5 is crucial for the stability of ORC as a whole. Only the ORC1-5 subunits are required for origin binding; ORC6 is essential for maintenance of pre-RCs once formed [
]. Interactions within ORC suggest that ORC2-3-6 may form a core complex []. DNA replication origin activation is positively regulated by ORC3 and ORC5 multi-mono-ubiquitylation catalysed by OBI1, which is important for origin firing [].ORC homologues have been found in various eukaryotes, including fission yeast, insects, amphibians, and humans [
]. This group represents an origin recognition complex, subunit 4.
This entry represents the N-terminal domain found in NADH pyrophosphatase, which has a rudiment Nudix fold according to SCOP. This domain is also found in Nudix hydrolases, such as NudC, which has been shown to act as a NAD decapping enzyme [
].
This domain has a zinc ribbon structure and is found in proteins such as NAD-capped RNA hydrolases and NAD(P)H pyrophosphatases. It is often found between two NUDIX domains.
Members of this family are essential for the biosynthesis of sulpholipid-1 in prokaryotes. They adopt a structure that belongs to the sulphotransferase superfamily, consisting of a single domain with a core four-stranded parallel β-sheet flanked by α-helices [
].
DNA-directed RNA polymerases
(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric
enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme []. The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length [
]. The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors. RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs. Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.This family includes the DNA-directed RNA polymerases I, II, and III subunit RPABC4 (also known as RPC10 and ABC10-alpha) [
] and archaeal polymerase subunit P [].
ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain [
].The ABC module (approximately two hundred amino acid residues) is known to bind and hydrolyse ATP, thereby coupling transport to ATP hydrolysis in a large number of biological processes. The cassette is duplicated in several subfamilies. Its primary sequence is highly conserved, displaying a typical phosphate-binding loop: Walker A, and a magnesium binding site: Walker B. Besides these two regions, three other conserved motifs are present in the ABC cassette: the switch region which contains a histidine loop, postulated to polarise the attaching water molecule for hydrolysis, the signature conserved motif (LSGGQ) specific to the ABC transporter, and the Q-motif (between Walker A and the signature), which interacts with the gamma phosphate through a water bond. The Walker A, Walker B, Q-loop and switch region form the nucleotide binding site [,
,
].The 3D structure of a monomeric ABC module adopts a stubby L-shape with two distinct arms. ArmI (mainly β-strand) contains Walker A and Walker B. The important residues for ATP hydrolysis and/or binding are located in the P-loop. The ATP-binding pocket is located at the extremity of armI. The perpendicular armII contains mostly the alpha helical subdomain with the signature motif. It only seems to be required for structural integrity of the ABC module. ArmII is in direct contact with the TMD. The hinge between armI and armII contains both the histidine loop and the Q-loop, making contact with the gamma phosphate of the ATP molecule. ATP hydrolysis leads to a conformational change that could facilitate ADP release. In the dimer the two ABC cassettes contact each other through hydrophobic interactions at the antiparallel β-sheet of armI by a two-fold axis [,
,
,
,
,
].The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions [
]. Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette [,
]. More than 50 subfamilies have been described based on a phylogenetic and functional classification [,
,
].This domain is found on the C terminus of ABC-2 type transporter domains (
). It seems to be associated with the plant pleiotropic drug resistance (PDR) protein family of ABC transporters. Like in yeast, plant PDR ABC transporters may also play a role in the transport of antifungal agents [
] (see also ). The PDR family is characterised by a configuration in which the ABC domain is nearer the N terminus of the protein than the transmembrane domain [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein S9 is one of the proteins from the small ribosomal subunit. It belongs to the S9P family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacterial; algal chloroplast; cyanelle and archaeal S9 proteins; and mammalian, plant, and yeast mitochondrial ribosomal S9 proteins. These proteins adopt a β-α-β fold similar to that found in numerous RNA/DNA-binding proteins, as well as in kinases from the GHMP kinase family [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein S9 is one of the proteins from the small ribosomal subunit. It belongs to the S9P family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacterial; algal chloroplast; cyanelle and archaeal S9 proteins; and mammalian, plant, and yeast mitochondrial ribosomal S9 proteins. These proteins adopt a β-α-β fold similar to that found in numerous RNA/DNA-binding proteins, as well as in kinases from the GHMP kinase family [].This signature pattern covers a conserved region containing many charged residues and located in the central section of these proteins.
This domain occurs at the N terminus of Afi1 (Arf3-interacting protein 1), a protein necessary for vesicle trafficking in yeast. This domain is the interacting region of the protein which binds to Arf3. Afi1 is distributed asymmetrically at the plasma membrane and is required for polarized distribution of Arf3 but not of an Arf3 guanine nucleotide-exchange factor, Yel1p. However, Afi1 is not required for targeting of Arf3 or Yel1p to the plasma membrane. Afi1 functions as an Arf3 polarization-specific adapter and participates in development of polarity [
]. Although Arf3 is the homologue of human Arf6 it does not function in the same way, not being necessary for endocytosis or for mating factor receptor internalisation. In the S phase, however, it is concentrated at the plasma membrane of the emerging bud. Because of its polarized localisation and its critical function in the normal budding pattern of yeast, Arf3 is probably a regulator of vesicle trafficking, which is important for polarized growth.
Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome [
,
,
]. EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) [
].This entry represents a conserved domain usually found near the C terminus of EF1B-gamma chains, a peptide of 410-440 residues. The gamma chain appears to play a role in anchoring the EF1B complex to the beta and delta chains and to other cellular components.
Polynucleotide kinase 3 phosphatases play a role in the repair of single breaks in DNA induced by DNA-damaging agents such as gamma radiation and camptothecin [
].
These proteins catalyse the dephosphorylation of DNA 3'-phosphates. It is believed that this activity is important for the repair of single-strand breaks in DNA caused by radiation or oxidative damage. This region is often [
,
], but not always linked to a DNA 5'-kinase domain [,
]. As is common in this superfamily, DNA 3-phosphatase is magnesium dependent. A difference between this enzyme and other HAD-superfamily phosphatases is in the third conserved catalytic motif which usually contains two conserved aspartate residues believed to be involved in binding the magnesium ion. Here, the second aspartate is usually replaced by an arginine residue which may indicate an interaction with the phosphate backbone of the substrate. Alternatively, there is an additional conserved aspartate downstream of the usual site which may indicate a slightly different fold in this region.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
This entry represents sucrose synthase an enzyme that despite its name, generally uses rather produces sucrose. Sucrose plus UDP (or ADP) becomes D-fructose plus UDP-glucose (or ADP-glucose), which is then available for cell wall (or starch) biosynthesis. The enzyme is homologous to sucrose phosphate synthase, which catalyses the penultimate step in sucrose synthesis. Sucrose synthase is found, so far, exclusively in plants and cyanobacteria [
].
Sucrose synthases catalyse the synthesis of sucrose
in the following reaction:
UDP-glucose + D-fructose = UDP + sucrose
This family includes the bulk of the sucrose synthase protein. However the carboxyl terminal region of the sucrose synthases belongs to the glycosyl transferase family . This enzyme is found mainly in plants but also appears in cyanobacteria.
This domain is found in the N terminus of some argonaut proteins. Argonaut (AGO) proteins are involved in RNA-mediated post-transcriptional gene silencing [
].
This entry represent the transmembrane protein 18 (TMEM18). In humans, TMEM18 is a transcription repressor and a sequence-specific ssDNA and dsDNA binding protein, with preference for GCT end CTG repeats [
]. It enhances the tropism of neural stem cells for glioma cells [].
This entry represents the methionine S-methyltransferase (
) family, which catalyse the S-methylmethionine (SMM) biosynthesis from adenosyl-L-homocysteine (AdoMet) and methionine [
]. All flowering plants produce S-methylmethionine (SMM) from Met and have a separate mechanism to convert SMM back to Met. The functions of SMM and the reasons for its interconversion with Met are unknown []. Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [,
,
]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM []. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [,
,
]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [,
,
]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Cytochrome C biogenesis protein, transmembrane domain
Type:
Domain
Description:
This entry represents the transmembrane domain of Cytochrome C biogenesis proteins also known as disulphide interchange proteins, such as DsbD from E. coli and DipZ from Mycobacterium. These proteins posses a protein disulphide isomerase like domain that is not found within the aligned region of this family.DsbA and DsbC, periplasmic proteins of E. coli, are two key players involved in disulphide bond formation. DsbD generates a reducing source in the periplasm, which is required for maintaining proper redox conditions [
]. DipZ is essential for maintaining cytochrome c apoproteins in the correct conformations for the covalent attachment of haem groups to the appropriate pairs of cysteine residues [].
