Inosine-uridine preferring nucleoside hydrolase (
) (IU-nucleoside hydrolase or IUNH) is an enzyme first identified in protozoan [
] that catalyses the hydrolysis of all of the commonly occuring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates. This enzyme is important for these parasitic organisms, which are deficient in de novosynthesis of purines, to salvage the host purine nucleosides. IUNH from Crithidia fasciculata has been sequenced and characterised, it is an homotetrameric enzyme of subunits of 34 Kd. An histidine has been shown to be important for the catalytic mechanism, it acts as a proton donor to activate the hypoxanthine leaving group.
A highly conserved region located in the N-terminal extremity contains four conserved aspartates that have been shown [
] to be located in the active site cavity.IUNH is evolutionary related to a number of uncharacterised proteins from various biological sources.
Inosine-uridine preferring nucleoside hydrolase (
) (IU-nucleoside hydrolase or IUNH) is an enzyme first identified in protozoan [
] that catalyses the hydrolysis of all of the commonly occuring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates. This enzyme is important for these parasitic organisms, which are deficient in de novosynthesis of purines, to salvage the host purine nucleosides. IUNH from Crithidia fasciculata has been sequenced and characterised, it is an homotetrameric enzyme of subunits of 34 Kd. An histidine has been shown to be important for the catalytic mechanism, it acts as a proton donor to activate the hypoxanthine leaving group.
A highly conserved region located in the N-terminal extremity contains four conserved aspartates that have been shown [
] to be located in the active site cavity.IUNH is evolutionary related to a number of uncharacterised proteins from various biological sources.This entry represents the structural domain of IUNH.
ECF (energy-coupling factor) transporters are a subgroup of ABC (ATP-binding cassette) transporters involved in the uptake of vitamins and micronutrients in prokaryotes [
]. ECF transporters are protein complexes consisting of a conserved module (two peripheral ATPases and the integral membrane protein EcfT) and a non-conserved integral membrane protein responsible for substrate specificity (S-component) []. This entry represents the transmembrane component from a number of ECF transporters, including cobalt-specific transporter CbiQ, and nickel-specific transporter NikQ [
]. It also includes uncharacterised eukaryotic proteins.
This entry describes proteins of unknown function. Structures for two of these proteins, YggU from Escherichia coli and MTH637 from the archaea Methanobacterium thermoautotrophicum, have been determined; they have a core 2-layer alpha/beta structure consisting of beta(2)-loop-α-β(2)-alpha [
,
].
Extensins shares protein sequence similarity with hydroxyproline-rich glycoproteins (HRGPs) found in the plant extracellular matrix. They form a structural component which strengthens the primary cell wall; they can account for up to 20% of the dry weight of the cell wall. The key to the role of HRGPs in cell wall self-assembly and cell extension lies in their chemistry, which is dependent on extensive post-translational modifications (PTMs): hydroxylation, glycosylation, and cross-linking. Repetitive peptide motifs characterise HRGPs [
].
Exportin-2, also known as CAS, is an export receptor for importin-alpha [
]. It binds strongly to importin alpha only in the presence of RanGTP, forming an importin alpha/CAS/RanGTP complex. Exportin-2 mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates have been released into the nucleoplasm [].This domain is found in exportin-2 and related proteins, such as exportin-7/8. This domain contains HEAT repeats.
This entry contains some of the solute carrier family 35 members, including SLC35F1, SLC35F2 and SLC35F6. In humans, SLC35F6 is involved in the maintenance of mitochondrial membrane potential in pancreatic ductal adenocarcinoma (PDAC) cells. It promotes pancreatic ductal adenocarcinoma (PDAC) cell growth and may play a role as a nucleotide-sugar transporter [
].
Non-structural maintenance of chromosome element 4, C-terminal
Type:
Domain
Description:
Nse4 is the kleisin component of the Smc5/6 DNA repair complex. It bridges the heads of Smc5 and Smc6 [
]. This entry represents the highly conserved C-terminal domain which interacts with the head domain of Smc5 [].
Proteins in the NSE4/EID (Non-structural maintenance of chromosomes element 4/EP300-interacting inhibitor of differentiation 3) family are components of the Smc5/6 complex that is involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components [
,
,
]. In human, it acts as a repressor of nuclear receptor-dependent transcription possibly by interfering with CREBBP-dependent coactivation. It may function as a coinhibitor of other CREBBP/EP300-dependent transcription factors []. Interestingly, there is a single NSE4 gene in most eukaryotes up to non-placental mammals while there are several NSE4/EID copies in placental mammals [
]. In humans, there are two NSE4 proteins, NSE4a and NSE4b/EID3. They contain both N and C-terminal kleisin domains. Their N-terminal domain binds to SMC6 neck and bridges it to the SMC5 head [] and to the Nse3 (another SMC5-6 complex subunit) pocket [], which seems to increased the stability of the ATP-free SMC5/6 complex.
This superfamily represents a structural domain which consists of three α-helices, including the arfaptin homology (AH) domain and the BAR (Bin-Amphiphysin-Rvs) domain.The arfaptin homology (AH) domain is a protein domain found in a range of proteins, including arfaptins, protein kinase C-binding protein PICK1 [
] and mammalian 69kDa islet cell autoantigen (ICA69) []. The AH domain of arfaptin has been shown to dimerise and to bind Arf and Rho family GTPases [,
], including ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The AH domain consists of three α-helices arranged as an extended antiparallel α-helical bundle. Two arfaptin AH domains associate to form a highly elongated, crescent-shaped dimer [,
].Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs) domain, which is required for their in vivofunction and their ability to tubulate membranes [
]. The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases.
Endocytosis and intracellular transport involve several mechanistic steps:
(1) for the internalisation of cargo molecules, the membrane needs to bend to form a vesicular structure, which requires membrane curvature and a rearrangement of the cytoskeleton; (2) following its formation, the vesicle has to be pinched off the membrane; (3) the cargo has to be subsequently transported through the cell and the vesicle must fuse with the correct cellular compartment.Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs)-domain, which is required for their in vivofunction and their ability to tubulate membranes [
]. The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases.
A number of phosphatidyltransferases, which are all involved in phospholipid biosynthesis and that share the property of catalysing the displacement of CMP from a CDP-alcohol by a second alcohol with formation of a phosphodiester bond and concomitant breaking of a phosphoride anhydride bond share a conserved sequence region [
,
]. These enzymes are proteins of 200 to 400 amino acid residues. The conserved region contains three aspartic acid residues and is located in the N-terminal section of the sequences.
Formate-tetrahydrofolate ligase, FTHFS, conserved site
Type:
Conserved_site
Description:
Formate--tetrahydrofolate ligase (
) (formyltetrahydrofolate synthetase) (FTHFS) is one of the enzymes
participating in the transfer of one-carbon units, an essential element of various biosynthetic pathways. FTHFS catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO2fixation (acetogenesis) and the glycine synthase/reductase pathways of purinolysis. The key physiological role of this enzyme in acetogens is to catalyze the formylation of tetrahydrofolate, an initial step in the reduction of carbon dioxide and other one-carbon precursors to acetate. In purinolytic organisms, the enzymatic reaction is reversed, liberating formate from 10-formyltetrahydrofolate with concurrent production of ATP [
,
]. In many of these processes the transfers of one-carbon units are mediated by the coenzyme tetrahydrofolate (THF). In eukaryotes the FTHFS activity is expressed by a multifunctional enzyme, C-1-tetrahydrofolate synthase (C1-THF synthase), which also catalyses the dehydrogenase and cyclohydrolase activities. Two forms of C1-THF synthases are known [], one is located in the mitochondrial matrix, while the second one is cytoplasmic. In both forms the FTHFS domainconsists of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotes FTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues [
].The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica shows that the subunit is composed of three domains organised around three mixed β-sheets. There are two cavities between adjacent domains. One of them was identified as the nucleotide binding site by homology modelling. The large domain contains a seven-stranded β-sheet surrounded by helices on both sides. The second domain contains a five-stranded β-sheet with two α-helices packed on one side while the other two are a wall of the active site cavity. The third domain contains a four-stranded β-sheet forming a half-barrel. The concave side is covered by two helices while the convex side is another wall of the large cavity. Arg 97 is likely involved in formyl phosphate binding. The tetrameric molecule is relatively flat with the shape of the letter X, and the active sites are located at the end of the subunits far from the subunit interface [
].These signature patterns cover two regions that are almost perfectly conserved. The first one is a glycine-rich segment located in the N-terminal part of FTHFS and which could be part of an ATP-binding domain [
]. The second pattern is located in the central section of FTHFS.
Formate--tetrahydrofolate ligase (
) (formyltetrahydrofolate synthetase) (FTHFS) is one of the enzymes
participating in the transfer of one-carbon units, an essential element of various biosynthetic pathways. FTHFS catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO2fixation (acetogenesis) and the glycine synthase/reductase pathways of purinolysis. The key physiological role of this enzyme in acetogens is to catalyze the formylation of tetrahydrofolate, an initial step in the reduction of carbon dioxide and other one-carbon precursors to acetate. In purinolytic organisms, the enzymatic reaction is reversed, liberating formate from 10-formyltetrahydrofolate with concurrent production of ATP [
,
]. In many of these processes the transfers of one-carbon units are mediated by the coenzyme tetrahydrofolate (THF). In eukaryotes the FTHFS activity is expressed by a multifunctional enzyme, C-1-tetrahydrofolate synthase (C1-THF synthase), which also catalyses the dehydrogenase and cyclohydrolase activities. Two forms of C1-THF synthases are known [], one is located in the mitochondrial matrix, while the second one is cytoplasmic. In both forms the FTHFS domainconsists of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotes FTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues [
].The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica shows that the subunit is composed of three domains organised around three mixed β-sheets. There are two cavities between adjacent domains. One of them was identified as the nucleotide binding site by homology modelling. The large domain contains a seven-stranded β-sheet surrounded by helices on both sides. The second domain contains a five-stranded β-sheet with two α-helices packed on one side while the other two are a wall of the active site cavity. The third domain contains a four-stranded β-sheet forming a half-barrel. The concave side is covered by two helices while the convex side is another wall of the large cavity. Arg 97 is likely involved in formyl phosphate binding. The tetrameric molecule is relatively flat with the shape of the letter X, and the active sites are located at the end of the subunits far from the subunit interface [
].
Proteins resident in the lumen of the endoplasmic reticulum (ER) contain a C-terminal
tetrapeptide, commonly known as Lys-Asp-Glu-Leu (KDEL) in mammals and His-Asp-Glu-Leu(HDEL) in yeast (Saccharomyces cerevisiae) that acts as a signal for their retrieval from subsequent
compartments of the secretory pathway. The receptor for this signal is a ~26kDa Golgimembrane protein, initially identified as the ERD2 gene product in S. cerevisiae. The
receptor molecule, known variously as the ER lumen protein retaining receptor or the'KDEL receptor', is believed to cycle between the cis side of the Golgi apparatus andthe ER. It has also been characterised in a number of other species, including plants,
Plasmodium, Drosophila and mammals. In mammals, 2 highly related forms of thereceptor are known. The KDEL receptor is a highly hydrophobic protein of 220 residues; its sequence
exhibits 7 hydrophobic regions, all of which have been suggested to traverse themembrane [
]. More recently, however, it has been suggested that only 6 of theseregions are transmembrane (TM), resulting in both N- and C-termini on the cytoplasmic
side of the membrane.
Ribosomal protein S2, bacteria/mitochondria/plastid
Type:
Family
Description:
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 describes the bacterial, archaea, mitochondrial and chloroplast forms of ribosomal protein S2.
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 S2 proteins have been shown to belong to a family that includes 40S ribosomal subunit 40kDa proteins, putative laminin-binding proteins, NAB-1 protein and 29.3kDa protein from Haloarcula marismortui [
,
]. The laminin-receptor proteins are thus predicted to be the eukaryotic homologue of the eubacterial S2 risosomal proteins [].Ribosomal protein S2 (RPS2) are involved in formation of the translation initiation complex, where it might contact the messenger RNA and several components of the ribosome. It has been shown that in Escherichia coli RPS2 is essential for the binding of ribosomal protein S1 to the 30s ribosomal subunit. In humans, most likely in all vertebrates, and perhaps in all metazoans, the protein also functions as the 67kDa laminin receptor (LAMR1 or 67LR), which is formed from a 37kDa precursor, and is overexpressed in many tumors. 67LR is a cell surface receptor which interacts with a variety of ligands, laminin-1 and others. It is assumed that the ligand interactions are mediated via the conserved C terminus, which becomes extracellular as the protein undergoes conformational changes which are not well understood. Specifically, a conserved palindromic motif, LMWWML, may participate in the interactions. 67LR plays essential roles in the adhesion of cells to the basement membrane and subsequent signalling events, and has been linked to several diseases. Some evidence also suggests that the precursor of 67LR, 37LRP is also present in the nucleus in animals, where it appears associated with histones [
,
,
,
,
,
,
,
,
,
,
,
,
,
].
Ribosomal protein S2, flavodoxin-like domain superfamily
Type:
Homologous_superfamily
Description:
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 S2 proteins have been shown to belong to a family that includes 40S ribosomal subunit 40kDa proteins, putative laminin-binding proteins, NAB-1 protein and 29.3kDa protein from Haloarcula marismortui [
,
]. The laminin-receptor proteins are thus predicted to be the eukaryotic homologue of the eubacterial S2 risosomal proteins [].Ribosomal protein S2 (RPS2) are involved in formation of the translation initiation complex, where it might contact the messenger RNA and several components of the ribosome. It has been shown that in Escherichia coli RPS2 is essential for the binding of ribosomal protein S1 to the 30s ribosomal subunit. In humans, most likely in all vertebrates, and perhaps in all metazoans, the protein also functions as the 67kDa laminin receptor (LAMR1 or 67LR), which is formed from a 37kDa precursor, and is overexpressed in many tumors. 67LR is a cell surface receptor which interacts with a variety of ligands, laminin-1 and others. It is assumed that the ligand interactions are mediated via the conserved C terminus, which becomes extracellular as the protein undergoes conformational changes which are not well understood. Specifically, a conserved palindromic motif, LMWWML, may participate in the interactions. 67LR plays essential roles in the adhesion of cells to the basement membrane and subsequent signalling events, and has been linked to several diseases. Some evidence also suggests that the precursor of 67LR, 37LRP is also present in the nucleus in animals, where it appears associated with histones [,
,
,
,
,
,
,
,
,
,
,
,
,
].This entry represents a flavodoxin-like domain superfamily found in ribosomal protein S2.
This domain of approximately 100 residues is conserved from plants to humans. It is an anticodon-binding domain of a prolyl-tRNA synthetase [
]. It is found in Lms12 and homologues. Lsm12 is a putative RNA-binding and regulation protein that might be involved in mRNA degradation or tRNA splicing []. Recently, it was demonstrated that it binds nicotinic acid adenine dinucleotide phosphate (NAADP) that confers NAADP sensitivity to the two pore channel complex (TPCs) by acting as TPC accessory protein necessary for NAADP-evoked Ca2 release []. Therefore, further studies of the potential crosstalk between NAADP signaling and RNA regulation are required.
Gamma-glutamyl phosphate reductase (
) (GPR) is the enzyme that catalyses the second step in the biosynthesis of proline from glutamate, the NADP-dependent reduction of L-glutamate 5-phosphate into
L-glutamate 5-semialdehyde and phosphate. In bacteria (gene proA) and yeast [] (gene PRO2), GPR is a monofunctional protein, while in plants and mammals, it is a bifunctional enzyme (P5CS) [] that consists of two domains, an N-terminal glutamate 5-kinase domain () and a C-terminal GPR domain. In humans, the P5CS (ALDH18A1), an inner mitochondrial membrane enzyme, is essential to the de novo synthesis of the amino acids proline and arginine [
]. Tomato (Lycopersicon esculentum) has both the prokaryotic-like polycistronic operons encoding GK and GPR (PRO1, ALDH19) and the full-length, bifunctional P5CS (PRO2, ALDH18B1) [].This entry represents the C-terminal GPR domain of the gamma-glutamyl phosphate reductase.
Glutamate 5-kinase (
) catalyses the first step
in the biosynthesis of proline, the ATP-dependent phosphorylation of glutamate toglutamate 5-phosphate [
,
].This entry also includes N-acetylglutamate kinase (
), which catalyses the phosphorylation of N-acetylglutamate to N-acetylglutamate-5P in the pathway for arginine biosynthesis.
Glutamate 5-kinase (
) (gamma-glutamyl kinase) (GK) is the enzyme that catalyzes the first step in the biosynthesis of proline from glutamate, the ATP-dependent phosphorylation of L-glutamate into L-glutamate 5-phosphate.
In eubacteria (gene proB) and yeast [
] (gene PRO1), GK is a monofunctionalprotein, while in plants and mammals, it is a bifunctional enzyme (P5CS) [
]
that consists of two domains: a N-terminal GK domain and a C-terminal gamma-glutamyl phosphate reductase domain (
).
This entry represents a highly conserved glycine-and alanine-
rich region located in the central section of these enzymes.
L-glutamate 5-phosphotransferase, (gamma-glutamyl kinase, proB,
), catalyzes the first step in proline biosynthesis
ATP + L-glutamate = ADP + L-glutamate 5-phosphate.the product of which rapidly cyclises to 5-oxoproline and phosphate.This entry also includes delta-1-pyrroline-5-carboxylate synthase, an enzyme that in the N-terminal section belongs to the glutamate 5-kinase family. Glutamate 5-kinase hits the full length of this model, but delta 1-pyrroline-5-carboxylate synthetase does not hit the C-terminal 100 residues.
This family of membrane proteins transport nucleotide sugars from the cytoplasm into golgi vesicles. SLC35A1 (
) transports CMP-sialic acid, SLC35A2 (
) transports UDP-galactose and SLC35A3 (
) transports UDP-GlcNAc [
].
Members of this family are involved in the negative regulation of gluconeogenesis. They are required for both proteosome-dependent and vacuolar catabolite degradation of fructose-1,6-bisphosphatase (FBPase), where they probably regulate FBPase targeting from the FBPase-containing vesicles to the vacuole [
,
].
The branched-chain amino acids are synthesised by a common pathway that leads from pyruvate and alpha-ketobutyrate to valine and isoleucine, and a branch that leads from the immediate precursor of valine, alpha-ketoisovalerate, to leucine [
]. This pathway operates in archaea, bacteria, fungi and plants, but not mammals, making the enzymes suitable targets for the development of novel antibiotics and herbicides.Isopropylmalate synthase is the enzyme responsible for the the first committed step in the leucine branch of this biosynthetic pathway, the conversion of alpha-ketoisovalerate to alpha-isopropylmalate. It is either dimeric or tetrameric, depending on the organism, with a monomer molecular mass of 60-70kDa, a dependence on divalent metal ions for activity, and an alkaline pH optimum [
,
,
,
]. Like many other biosynthetic enzymes it is subject to feedback inhibition by the end product of the pathway, leucine. This entry represents the isopropylmalate synthase most commonly found in bacteria. A related form of this enzyme is found mainly in eukaryotes and some other bacteria (
). A homologous family in archaea may represent isozymes and/or related enzymes (
).
Alpha-isopropylmalate/homocitrate synthase, conserved site
Type:
Conserved_site
Description:
A number of enzymes have been shown to be functionally as well as
evolutionary related []. The nifV and leuA genes encode homocitrate synthase and alpha-isopropylmalate synthase, respectively
The N-terminal parts of NifV and LeuA from bacteria are highly similar to each other []. Homocitrate synthase () (gene nifV) is involved in the biosynthesis of the iron-molybdenum cofactor of nitrogenase and catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate into homocitrate. Alpha-isopropylmalate synthase (
) catalyses the first step in the biosynthesis of leucine, the condensation ofacetyl-CoA and alpha- ketoisovalerate to form 2-isopropylmalate synthase.
Pyruvate carboxylase (
) (PC), a member of the biotin-dependent enzyme family, is involved in gluconeogenesis by mediating the
carboxylation of pyruvate to oxaloacetate. Biotin-dependent carboxylase enzymes perform a two step reaction. Enzyme-bound biotin is first carboxylated by bicarbonate and ATP and the carboxyl group temporarily bound to biotin is subsequently transferred to an acceptor substrate such as pyruvate []. PC has three functional domains: a biotin carboxylase (BC) domain, a carboxyltransferase (CT) domain which perform the second part of the reaction and a biotinyl domain [,
]. The pyruvate binding to the CT active site induces a conformational change stabilised by the interaction of conserved Asp and Tyr residues in this domain which leads to the formation of the biotin binding pocket and ensures the efficient coupling of BC and CT domain reactions []. The mechanism by which the carboxyl group is transferred from the carboxybiotin to the pyruvate is not well understood.The pyruvate carboxyltransferase domain is also found in other pyruvate binding enzymes and acetyl-CoA dependent enzymes suggesting that this domain can be associated with different enzymatic activities.This domain is found towards the N-terminal region of various aldolase enzymes. This N-terminal TIM barrel domain [
] interacts with the C-terminal domain. The C-terminal DmpG_comm domain () is thought to promote heterodimerization with members of
to form a bifunctional aldolase-dehydrogenase [
].
This is the C-terminal regulatory (R) domain of alpha-isopropylmalate synthase, which catalyses the first committed step in the leucine biosynthetic pathway [
]. This domain, is an internally duplicated structure with a novel fold []. It comprises two similar units that are arranged such that the two helices pack together in the centre, crossing at an angle of 34 degrees, sandwiched between the two three-stranded, antiparallel β-sheets. The overall domain is thus constructed as a beta-α-β three-layer sandwich [].
MOZART1 or Mzt1 is a component of the gamma-tubulin complex and is required for its recruitment to the microtubule organizing centre in humans and yeast [
,
,
]. This function is conserved in plant homologues, known as gamma-tubulin complex protein 3 (GCP3)-interacting proteins (GIPs) [,
]. Studies in plant homologues GIP1 and GIP2 indicate that they play a major role in nuclear envelope shaping in both cycling and differentiated cells [] and that they are essential for centromere architecture [,
].
This entry represents a group of transmembrane proteins including TACAN (also known as TMEM120A) and TMEM120B. TACAN is an ion channel that contributes to sensing mechanical pain [
]. TACAN and TMEM120B may be required for efficient adipogenesis [].
ATP-dependent protease complexes are present in all three kingdoms of life, where they rid the cell of misfolded or damaged proteins and control the level of certain regulatory proteins. They include the proteasome in Eukaryotes, Archaea, and Actinomycetales and the HslVU (ClpQY, clpXP) complex in other eubacteria. Genes homologues to eubacterial HslU (ClpY, clpX) have also been demonstrated in to be present in the genome of trypanosomatid protozoa [
].The proteasome (or macropain) (
) [
,
,
,
,
] is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that is involved in an ATP/ubiquitin-dependent non-lysosomal proteolytic pathway. In eukaryotes the 20S proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Proteasome subunits can be classified on the basis of sequence similarities into two groups, alpha (A) and beta (B). The proteasome consists of four stacked rings composed of alpha/beta/beta/alpha subunits. There are seven different alpha subunits and seven different beta subunits []. Three of the seven beta subunits are peptidases, each with a different specificity. Subunit beta1c (MEROPS identifier T01.010) has a preference for cleaving glutaminyl bonds ("peptidyl-glutamyl-like"or "caspase-like"), subunit beta2c (MEROPS identifier T01.011) has a preference for cleaving arginyl and lysyl bonds ("trypsin-like"), and subunit beta5c (MEROPS identifier T01.012) cleaves after hydrophobic amino acids ("chymotrypsin-like") [
]. The proteasome subunits are related to N-terminal nucleophile hydrolases, and the catalytic subunits have an N-terminal threonine nucleophile.The prokaryotic ATP-dependent proteasome is coded for by the heat-shock locus VU (HslVU). It consists of HslV, a peptidase, and HslU (
), the ATPase and chaperone belonging to the AAA/Clp/Hsp100 family. The crystal structure of Thermotoga maritima HslV has been determined to 2.1-A resolution. The structure of the dodecameric enzyme is well conserved compared to those from Escherichia coli and Haemophilus influenzae [
,
].This family consists of the beta (or B type) subunits of the eukaryotic proteasome as well as the archaeal and bacterial proteasomes. These proteins belong to family T1 in the classification of peptidases.
The structure of tRNA(Ile)-lysidine synthetase consists of an N-terminal dinucleotide-binding fold domain (NTD), and a C-terminal globular domain (CTD). The structure of the NTD closely resembles that of a P-loop "N-type"ATP pyrophosphatase [
]. tRNA(Ile)-lysidine and 2-thiocytidine synthase both belong to the PP-loop superfamily [].
This entry represents proteins annotated as Ycf55. It is found encoded in the chloroplast genomes of algae, it is also found in plants and in the cyanobacteria. The function is unknown, though there are two completely conserved residues (L and D) that may be functionally important. As the family is exclusively found in phototrophic organisms it may play a role in photosynthesis. Some members of this family are predicted to be response regulators because they contain an N-terminal CheY-like receiver domain.
ORMDL family members include ORMDL1/2/3 from humans and their homologues, such as protein Orm1 and Orm2 from budding yeasts. ORMDLs may be involved in protein folding in the endoplasmic reticulum [
]. In budding yeast, Orm1 and Orm2 proteins mediate sphingolipid homeostasis [].
D-Pantothenate is synthesized via four enzymes from ketoisovalerate, which is an intermediate of branched-chain amino acid synthesis [
]. Pantoate-beta-alanine ligase, also know as pantothenate synthase, (PanC; ) catalyzes the formation of pantothenate from pantoate and alanine in the pantothenate biosynthesis pathway [
].PanC belongs to a large superfamily of nucleotidyltransferases that includes ATP sulfurylase (ATPS), phosphopantetheine adenylyltransferase (PPAT), and the amino-acyl tRNA synthetases. The enzymes of this family are structurally similar and share a dinucleotide-binding domain [
,
,
,
,
].
Members of this group include the archaeal protein Alba and eukaryotic Ribonuclease P subunits Pop7/Rpp20 and Rpp25. The Alba domain is closely related to the RNA-binding versions of the IF3-C fold such as YhbY and IF3-C. The eukaryotic lineages of the Alba family are principally involved in RNA metabolism, suggesting that the ancestral function of the IF3-C fold was related to RNA interaction [
].Alba has been shown to bind DNA and affect DNA supercoiling in a temperature dependent manner [
]. It is regulated by acetylation (alba = acetylation lowers binding affinity) by the Sir2 protein. Alba is proposed to play a role in establishment or maintenance of chromatin architecture and thereby in transcription repression. For further information see [].
This entry represents a group of arabinogalactan proteins (AGPs) from plants, and includes AGP16, AGP20, AGP22 and AGP41 [
]. These proteoglycans have been implicated in various processes associated with plant growth and development, including embryogenesis and cell proliferation
This entry represents the RNase H type-I domain.
Ribonuclease H (RNase H) (
) is a member of the ribonuclease family, which recognises and cleaves the RNA strand of RNA-DNA heteroduplexes. The enzyme is widely present in all three kingdoms of living organisms, including bacteria, archaea, and eukaryotes, and their counterpart domains are also found in reverse transcriptases (RTs) from retroviruses and retroelements [
]. RNases H are classified into two evolutionarily unrelated families, type-I and type-II RNase H, with common structural features of the catalytic domain but different range of substrates for enzymatic cleavage. There appears to be three evolutionarily distinct lineages of cellular Rnase H enzymes []. Type-I or RNase HI domains have been found in all Eukarya, one Archaea, many Eubacteria, a few non-LTR retroposons and all LTR retrotransposons. Type II enzymes consist of RNase HII (rnhB) and HIII (rnhC), which are homologous enzymes. RNase HII can be found in Archaea, Eubacteria and all Eukarya, while RNase HIII appears only in some Eubacteria. In eukaryotes and all Archaea, RNase HII enzymes may constitute the bulk of all Rnase H activity, while the reverse is true in Eubacteria like E. coli where RNase HI is the major source of RNH activity [,
,
]. All LTR retrotransposons acquired an enzymatically weak RNase H domain that is missing an important catalytic residue found in all other RNase H enzymes. Vertebrate retroviruses appear to have reacquired their RNase H domains, which are catalytically more active, but their ancestral RNase H domains (found in other LTR retrotransposons) have degenerated to give rise to the tether domain unique to vertebrate retrovirus []. Reverse transcriptase (RT) is a modular enzyme carrying polymerase and ribonuclease H (RNase H) activities in separable domains. Retroviral RNase H is synthesised as part of the POL polyprotein that contains an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. RNAse H activity requires the presence of divalent cations (Mg2+ or Mn2+) that bind its active site. The main element of the RNase H-like catalytic core is a β-sheet comprising five β-strands, ordered 3-2-1-4-5, where the β-strand 2 is antiparallel to the other β-strands. On both sides the central β-sheet is flanked by α-helices, the number of which differs between related enzymes. The catalytic residues for RNase H enzymatic activity (three aspartic acid and one glutamic acid residue) are invariant across all RNase H domains [,
,
,
,
,
,
].
This entry includes a group of oil body associated proteins (OBAPs) from plants and some uncharacterised proteins from fungi and bacteria. The plant obap proteins are predominantly expressed during embryo development and may be involved in the stability of oil bodies [
].
This entry represents the N-terminal domain of SS18 and related proteins.
SSXT (also known as SS18) appears to function synergistically with RBM14 as a transcriptional coactivator [
].The SSXT protein is involved in synovial sarcoma in humans. A SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18) (p11;q11) is characteristic of synovial sarcomas. This translocation fuses the SSXT (SYT) gene from chromosome 18 to either of two homologous genes at Xp11, SSX1 or SSX2 [
].The SS18 family also includes SS18-like proteins 1 and 2, and GRF1-interacting factors from plants [
]. SS18-like protein 1 is a transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons [,
].
Two different types of thiolase [
,
,
] are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase () and 3-ketoacyl-CoA thiolase (
). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.
In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction.Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases [
].
Two different types of thiolase [
,
,
] are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase () and 3-ketoacyl-CoA thiolase (
). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.
In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction.Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases [
].
This presumed domain is functionally uncharacterised. This domain is found in eukaryotes. This domain is about 120 amino acids in length. This domain has a conserved CDCGGWD sequence motif.
GTP cyclohydrolase I (
) catalyses the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP [
]. This reaction is the first step in the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in vertebrates, and of pteridine-containing pigments in insects. The comparison of the sequence of the enzyme from bacterial and eukaryotic sources shows that the structure of this enzyme has been extremely well conserved throughout evolution [].
GTP cyclohydrolase I (
) catalyses the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP [
]. This reaction is the first step in the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in vertebrates, and of pteridine-containing pigments in insects. The comparison of the sequence of the enzyme from bacterial and eukaryotic sources shows that the structure of this enzyme has been extremely well conserved throughout evolution [].This entry represents a common fold found in GTP cyclohydrolase I [
].
This entry includes ATPase complex subunit ATP10, mostly from yeasts and plants. In budding yeasts, ATP10 is a mitochondria protein that is essential for the assembly of the mitochondrial F1-F0 complex [
]. It assists assembly of Atp6 into the F0 unit of the yeast mitochondrial ATPase [].
Active extrusion is a common mechanism for the detoxification of heavy metals, drugs and antibiotics in bacteria, protozoa and mammals. This is particularly important for arsenic extrusion because of its prevalence in the environment and its potential to cause health and environmental problems. In prokaryotes, arsenic detoxification is accomplished by chromosomal and plasmid-borne operon-encoded efflux systems. ArsA from Escherichia coli is the catalytic subunit of the ArsAB extrusion pump, providing resistance to arsenite and antimonite. This pump consists of a soluble ATPase (ArsA) and a membrane channel (ArsB). Maintenance of a low intracellular concentration of oxidation produces resistance to the toxic agents. A third protein, ArsC, expands the substrate specificity to allow for arsenate resistance. ArsC reduces arsenate to arsenite, which is subsequently pumped out of the cell [
]. ArsA contains two nucleotide-binding sites (NBSs) and a binding site for arsenic or antimony. Binding of metalloids to the pump stimulates the ATPase activity [].Homologues of the bacterial ArsA ATPase are found in eukaryotes, where they
have several recognised functions unrelated to arsenic resistance []. Caenorhabditis elegans homologue Asna-1 is required for defence against arsenite and antimonite toxicity [], and may be also involved in insulin signaling []. The homologue in yeast, GET3/Arr4, is part of the GET complex and not only is involved in stress tolerance to metals and heat [], but also specifically recognises transmenbrane domains of tail-anchored (TA) proteins destined for the secretory pathway []. Archaeal GET3 homologues have also been discovered, suggesting that that archaea may possess a TA protein targeting pathway similar to that in eukaryotes [,
].
This entry represents a conserved domain, which is sometimes repeated, in an anion-transporting ATPase [
,
]. The ATPase is involved in the removal of arsenate, antimonite, and arsenate from the cell. The entry also matches some sequences from the Mrp/NBP35 ATP-binding proteins family.
Phosphatidylcholine-hydrolysing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolysing PLD is a homologue of cardiolipin synthase, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, and/or asparagine residues which may contribute to the active site aspartic acid. An Escherichia coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs [
,
,
,
].
Phospholipase D (PLD) catalyses the hydrolysis of the phosphodiester bond of glycerophospholipids to generate phosphatidic acid and a free head group. Phospholipase D activities have been detected in simple to complex organisms from viruses and bacteria to yeast, plants, and mammals [
]. In higher organisms, PLD specifically catalyzes the hydrolysis of phosphatidylcholine (PC) to phosphatidic acid (PA) and choline and is activated in response to stimulators of vesicle transport, endocytosis, exocytosis, cell migration, and mitosis.This entry represents the C-terminal domain of eukaryotic phospholipase D. The domain is approximately 70 amino acids in length and contains a conserved FPD sequence motif.
Phospholipase D (PLD) catalyses the hydrolysis of the phosphodiester bond of glycerophospholipids to generate phosphatidic acid and a free head group. Phospholipase D activities have been detected in simple to complex organisms from viruses and bacteria to yeast, plants, and mammals [
]. In higher organisms, PLD specifically catalyzes the hydrolysis of phosphatidylcholine (PC) to phosphatidic acid (PA) and choline and is activated in response to stimulators of vesicle transport, endocytosis, exocytosis, cell migration, and mitosis.There are two mammalian phospholipase D genes whose products (PLD1 and PLD2) are alternatively spliced. Both forms have two highly conserved HKD motifs that are essential for catalysis and dimerisation [
]. It has now been observed that there are abnormalities in PLD expression and activity in many human cancers [].Most bacteria use an enzyme belonging to the phospholipase D family as cardiolipin synthase. In contrast, eukaryotes and most actinobacteria use a cardiolipin synthase of the CDP-alcohol phosphatidyltransferase family [
].
Ubiquitin related modifier 1 (Urm1) is a ubiquitin related protein that modifies proteins in the yeast ubiquitin-like urmylation pathway [
]. Structural comparisons and phylogenetic analysis of the ubiquitin superfamily has indicated that Urm1 has the most conserved structural and sequence features of the common ancestor of the entire superfamily []. Urm1 acts as a sulfur carrier required for 2-thiolation of mcm5S2U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln) [].
Phospho-N-acetylmuramoyl-pentapeptide-transferase (
) (MraY) is a bacterial enzyme responsible for the formation of the first lipid intermediate of the cell wall peptidoglycan synthesis [
]. It catalyses the formation of undecaprenyl-pyrophosphoryl-N-acetylmuramoyl-pentapeptide from UDP-MurNAc-pentapeptide and undecaprenyl-phosphate. MraY is an integral membrane protein with probably ten transmembrane domains. It belongs to family 4 of glycosyl transferases. Homologues of MraY have been found in archaebacteria Methanobacterium thermoautotrophicum and in Arabidopsis thaliana (Mouse-ear cress).
This entry represents a family of UDP-GlcNAc/MurNAc: polyisoprenol-P GlcNAc/MurNAc-1-P transferases. Members of the family include eukaryotic N-acetylglucosamine-1-phosphate transferases, which catalyse the conversion of UDP-N-acteyl-D-glucosamine and dolichyl phosphate to UMP and N-acetyl-D-glucosaminyl-diphosphodolichol in the glycosylation pathway;
and bacterial phospho-N-acetylmuramoyl-pentapeptide-transferases, which catalyse the first step of the lipid cycle reactions in the biosynthesis of cell wall peptidoglycan.
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 entry represents the eukaryotic 60S ribosomal protein L18a [
] and L20 [] from eukaryotes. Rat ribosomal protein L18 is homologous to Xenopus laevis L14 [].
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 S11 [
] plays an essential role in selecting the correct tRNA in protein biosynthesis. It is located on the large lobe of the small ribosomal subunit. On the basis of sequence similarities, S11 belongs to a family of bacterial, archaeal and eukaryotic ribosomal proteins. This entry represents a small conserved site found in S11 ribosomal proteins.
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 S11 [
] plays an essential role in selecting the correct tRNA in protein biosynthesis. It is located on the large lobe of the small ribosomal subunit. S14 is the eukaryotic homologue of S11; they constitute the uS11 family that includes bacterial, archaeal and eukaryotic proteins [].
Glutamate synthase (GltS) is a complex iron-sulphur flavoprotein that catalyses the reductive synthesis of L-glutamate from 2-oxoglutarate and L-glutamine via intramolecular channelling of ammonia, a reaction in the bacterial, yeast and plant pathways for ammonia assimilation []. GltS is a multifunctional enzyme that functions through three distinct active centres carrying out multiple reaction steps: L-glutamine hydrolysis, conversion of 2-oxoglutarate into L-glutamate, and electron uptake from an electron donor. The active centres are synchronised to avoid the wasteful consumption of L-glutamine []. There are three classes of GltS, which share many functional properties: bacterial NADPH-dependent GltS, ferredoxin-dependent GltS from photosynthetic cells, and NAD(P)H-dependent GltS from yeast, fungi and lower animals.The dimeric alpha subunits each consist of four domains: N-terminal amidotransferase domain, the central domain, the FMN binding domain and the C-terminal domain. The C-terminal domain forms a right-handed β-helix that comprises seven helical turns [
]. Each helical turn has a sharp bend that is associated with a repeated sequence motif consisting of G-XX-G-XXX-G. This domain does not contain any residues directly involved in catalysis, but has a crucial structural role.This domain is also found in proteins such as subunit C of formylmethanofuran dehydrogenase, which catalyses the first step in methane formation from carbon dioxide in methanogenic archaea. There are two isoenzymes of formylmethanofuran dehydrogenase: a tungsten-containing isoenzyme (FwdC) and a molybdenum-containing isoenzyme (FmdC). The tungsten isoenzyme is constitutively transcribed, whereas transcription of the molybdenum operon is induced by molybdate [
].
This entry represents the DEP (Dishevelled, Egl-10 and Pleckstrin) domain, a globular domain of about 80 residues that is found in over 50 proteins involved in G-protein signalling pathways. It was named after the three proteins it was initially found in:Dishevelled (Dsh and Dvl), which play a key role in the transduction of the Wg/Wnt signal from the cell surface to the nucleus; it is a segment polarity protein required to establish coherent arrays of polarized cells and segments in embryos, and plays a role in wingless signalling.Egl-10, which regulates G-protein signalling in the central nervous system. Pleckstrin, the major substrate of protein kinase C in platelets; Pleckstrin contains two PH domains flanking the DEP domain.Mammalian regulators of G-protein signalling also contain these domains, and regulate signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving them into their inactive GDP-bound form. It has been proposed that the DEP domain could play a selective role in targeting DEP domain-containing proteins to specific subcellular membranous sites, perhaps even to specific G protein-coupled signaling pathways [
,
]. Nuclear magnetic resonance spectroscopy has revealed that the DEP domain comprises a three-helix bundle, a β-hairpin 'arm' composed of two β-strands and two short β-strands in the C-terminal region [].
A small region that overlaps with a nuclear localization signal and binds to the RNA primer contains three aspartates that are essential for catalysis. Sequence and secondary structure comparisons of regions surrounding these aspartates with sequences of other polymerases revealed a significant homology to the palm structure of DNA polymerase beta, terminal deoxynucleotidyltransferase and DNA polymerase IV of Saccharomyces cerevisiae, all members of the family X of polymerases. This homology extends as far as cca: tRNA nucleotidyltransferase and streptomycin adenylyltransferase, an antibiotic resistance factor [
,
].Proteins containing this domain include kanamycin nucleotidyltransferase (KNTase) which is a plasmid-coded enzyme responsible for some types of bacterial resistance to aminoglycosides. KNTase inactivates antibiotics by catalysing the addition of a nucleotidyl group onto the drug. In experiments, Mn2+ strongly stimulated this reaction due to a 50-fold lower Ki for 8-azido-ATP in the presence of Mn2+. Mutations of the highly conserved
Asp residues 113, 115, and 167, critical for metal binding in the catalytic domain of bovine poly(A) polymerase, led to a strongreduction of cross-linking efficiency, and Mn2+ no longer stimulated the reaction. Mutations in the region of the "helical turn motif"(a domain binding the triphosphate moiety of the nucleotide) and in the suspected nucleotide-binding helix of bovine poly(A) polymerase
impaired ATP binding and catalysis. The results indicate that ATP is bound in part by the helical turn motif and in part by a region thatmay be a structural analogue of the fingers domain found in many polymerases.
Eukaryotic translation initiation factor 4E (eIF-4E), conserved site
Type:
Conserved_site
Description:
Eukaryotic translation initiation factor 4E (eIF-4E) [
] is a protein thatbinds to the cap structure of eukaryotic cellular mRNAs. eIF-4E recognises and binds
the 7-methylguanosine-containing (m7Gppp) cap during an early step in the initiationof protein synthesis and facilitates ribosome binding to a mRNA by inducing the unwinding
of its secondary structures. eIF-4E is a conserved protein of about 25kDa. Site directed mutagenesis experiments have shown [
] that a tryptophan in the central part of the sequence of human eIF-4E seems to be implicated in cap-binding. The signature pattern used in this entry includes this tryptophan.
Eukaryotic translation initiation factor 4E (eIF-4E) [
] is a protein thatbinds to the cap structure of eukaryotic cellular mRNAs. eIF-4E recognises and binds
the 7-methylguanosine-containing (m7Gppp) cap during an early step in the initiationof protein synthesis and facilitates ribosome binding to a mRNA by inducing the unwinding
of its secondary structures. A tryptophan in the central part of the sequence of humaneIF-4E seems to be implicated in cap-binding [
].
Eukaryotic translation initiation factor 4E (eIF-4E) [
] is a protein thatbinds to the cap structure of eukaryotic cellular mRNAs. eIF-4E recognises and binds
the 7-methylguanosine-containing (m7Gppp) cap during an early step in the initiationof protein synthesis and facilitates ribosome binding to a mRNA by inducing the unwinding
of its secondary structures. A tryptophan in the central part of the sequence of humaneIF-4E seems to be implicated in cap-binding [
].This entry includes a group of eIF4E-like protein. These proteins consist of a curved eight-stranded antiparallel β-sheet, decorated with three helices on the convex face and three smaller helices inserted in connecting loops [
].
This entry represents the PITH domain (derived from Proteasome-Interacting THioredoxin). The protein Txnl1, which is a probable component of the 32kDa 26S proteasome, uses its C-terminal PITH domain to associate specifically with the 26S proteasome [
].The PITH domain is dominated by a jelly roll β-sandwich structure. The β-sandwich is formed by face-to-face packing of two anti-parallel β-sheets. Another two-stranded β-sheet seals off one end of the β-barrel [
,
].
Phosphorylases with this domain include:Purine nucleoside phosphorylase (
) (PNP) from most bacteria (gene deoD), which catalyses the cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules [
].Uridine phosphorylase (
) (UdRPase) from bacteria (gene udp) and mammals, which catalyses the cleavage of uridine into uracil and ribose-1-phosphate, the products of the reaction are used either as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis [
].5'-methylthioadenosine phosphorylase (
) (MTA phosphorylase) from Sulfolobus solfataricus [
].Purine nucleoside phosphorylase (
) (PNP) from mammals as well as from some bacteria (gene deoD). This enzyme catalyzes the cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules [
].5'-methylthioadenosine phosphorylase (
) (MTA phosphorylase) from eukaryotes [
].
Prokaryotes contain a single DNA-dependent RNA polymerase (RNAP;
) that is responsible for the transcription of all genes, while eukaryotes have three classes of RNAPs (I-III) that transcribe different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. Certain subunits of RNAPs, including RPB5 (POLR2E in mammals), are common to all three eukaryotic polymerases. RPB5 plays a role in the transcription activation process. Eukaryotic RPB5 has a bipartite structure consisting of a unique N-terminal region (
), plus a C-terminal region that is structurally homologous to the prokaryotic RPB5 homologue, subunit H (gene rpoH) [
,
,
,
].This entry represents prokaryotic subunit H and the C-terminal domain of eukaryotic RPB5, which share a two-layer alpha/beta fold, with a core structure of beta/alpha/beta/alpha/beta(2).
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
, ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents UBP-type zinc finger domains, which display some similarity with the Zn-binding domain of the insulinase family. The UBP-type zinc finger domain is found only in a small subfamily of ubiquitin C-terminal hydrolases (deubiquitinases or UBP) [
,
], All members of this subfamily are isopeptidase-T, which are known to cleave isopeptide bonds between ubiquitin moieties.Some of the proteins containing an UBP zinc finger include:Homo sapiens (Human) deubiquitinating enzyme 13 (UBPD)Human deubiquitinating enzyme 5 (UBP5)Dictyostelium discoideum (Slime mold) deubiquitinating enzyme A (UBPA)Saccharomyces cerevisiae (Baker's yeast) deubiquitinating enzyme 8 (UBP8)Yeast deubiquitinating enzyme 14 (UBP14)
Ndc1 is a nucleoporin protein that is a component of the Nuclear Pore Complex, and, in fungi, also of the Spindle Pole Body. It consists of six transmembrane segments, three luminal loops, both concentrated at the N terminus and cytoplasmic domains largely at the C terminus, all of which are well conserved.
This entry includes COV1 from Arabidopsis and uncharacterised proteins from bacteria and archaea. COV1 is an integral membrane protein involved in the regulation of vascular patterning in the stem, probably by negatively regulating the differentiation of vascular tissue [
].
Obg subfamily proteins (also known as ObgE, YhbZ and CgtA) are conserved P- loop GTPases, that are involved in a wide range of cellular processes, including sporulation, cellular differentiation, ribosome assembly, DNA replication, chromosome segregation, and stringent response in eubacteria and plant chloroplasts. Obg subfamily proteins have three domains: the Obg fold, the G domain, and the Obg C-terminal (OCT) domain. A potential role of the OCT domain in the regulation of the nucleotide-binding state has been suggested [
,
,
]. The OCT domain structure contains a four-stranded beta sheet and three alpha helices flanked by an additional beta strand []. This entry represents the OCT domain.
A widespread family of GTP-binding proteins has been recently characterised
[,
]. The function of the proteins that belong to this family is not yet known. They are polypeptides of about 40 to 48kDa which contain the five small sequenceelements characteristic of GTP-binding proteins [
]. As a signature pattern wasselected the region that correspond to the ATP/GTP B motif (also called G-3 in
GTP-binding proteins).
This entry describes a universal, mostly one-gene-per-genome GTP-binding protein that associates with ribosomal subunits and appears to play a role in ribosomal RNA maturation. Mutations in this gene are pleiotropic, but it appears that effects on cellular functions such as chromosome partition may be secondary to the effect on ribosome structure.This is an essential GTPase which binds GTP, GDP and ppGpp with moderate affinity (with a twofold preference for GDP over GTP); shows high guanine nucleotide exchange rate constants for both nucleotides, and has a relatively low GTP hydrolysis rate. Deletion of the N terminus makes a protein that is non-functional in vivo but which retains nucleotide binding and GTPase activity. Required for cell cycle progression from G1 to S phase and for DNA replication [
].
The N-terminal domain of GTPase Obg has the OBG fold, which is formed by three glycine-rich regions inserted into a small 8-stranded β-sandwich. These regions form six left-handed collagen-like helices packed and H-bonded together.Several proteins have recently been shown to contain the 5 structural motifs characteristic
of GTP-binding proteins []. These include murine DRG protein; GTP1 proteinfrom Schizosaccharomyces pombe; OBG protein from Bacillus subtilis; and several others.
Although the proteins contain GTP-binding motifs and are similar to each other, they donot share sequence similarity to other GTP-binding proteins, and have thus been classed
as a novel group, the GTP1/OBG family. As yet, the functions of these proteins is uncertain,but they have been shown to be important in development and normal cell metabolism
[,
].
Glutaredoxins [
,
,
], also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system [].Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond [
]. It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates [
,
,
,
]. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed [
] that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.This entry represents a conserved region including the active site of this enzyme.
Utp23 share homology with PINc domain protein Fcf1. They are components of the small subunit processome (SSU) that are involved in rRNA-processing and ribosome biogenesis [
,
]. Depletion of yeast Fcf1 and Fcf2 leads to a decrease in synthesis of the 18S rRNA and results in a deficit in 40S ribosomal subunits [
].
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 [
,
].The ribosomal protein family L20, from the large (50S) subunit, contains members from eubacteria, as well as their mitochondrial and plastid homologs. L20 is an assembly protein, required for the first in vitro reconstitution step of the 50S ribosomal subunit, but does not seem to be essential for ribosome activity. L20 has been shown to partially unfold in the absence of RNA, in regions corresponding to the RNA-binding sites. L20 represses the translation of its own mRNA via specific binding to two distinct mRNA sites, in a manner similar to the L20 interaction with 23S ribosomal RNA [
,
,
,
,
,
,
].
Aldehyde oxidase/xanthine dehydrogenase, first molybdopterin binding domain
Type:
Domain
Description:
Aldehyde oxidase (AOX
) catalyses the conversion of an aldehyde in the presence of oxygen and water to an acid and hydrogen peroxide. The enzyme is a homodimer, and requires FAD, molybdenum and two 2FE-2S clusters as cofactors. Xanthine dehydrogenase (XDH
) catalyses the hydrogenation of xanthine to urate, and also requires FAD, molybdenum and two 2FE-2S clusters as cofactors. This activity is often found in a bifunctional enzyme with xanthine oxidase (
) activity too. The enzyme can be converted from the dehydrogenase form to the oxidase form irreversibly by proteolysis or reversibly through oxidation of sulfhydryl groups [
].The aldehyde oxido-reductase (Mop) from the sulphate reducing anaerobic Gram-negative bacterium Desulfovibrio gigas is a homodimer of 907 amino acid residues subunits and is a member of the xanthine oxidase family. The protein contains a molybdopterin cofactor (Mo-co) and two different [2Fe-2S] centres. It is folded into four domains of which the first two bind the iron sulphur centres and the last two are involved in Mo-co binding. Mo-co is a molybdenum molybdopterin cytosine dinucleotide. Molybdopterin forms a tricyclic system with the pterin bicycle annealed to a pyran ring. The molybdopterin dinucleotide is deeply buried in the protein. The cis-dithiolene group of the pyran ring binds the molybdenum, which is coordinated by three more (oxygen) ligands [].This domain represents the first molybdopterin cofactor (Mo-Co) binding domain.
Oxidoreductases, that also bind molybdopterin, have essentially no similarity outside this common domain.
They include aldehyde oxidase (), that converts an aldehyde and water to an acid and hydrogen peroxide, and xanthine dehydrogenase (
), that converts xanthine to urate. These enzymes require molybdopterin and FAD as cofactors and have and two 2FE-2S clusters. Another enzyme that contains this domain is the Pseudomonas thermocarboxydovorans carbon monoxide oxygenase.
Aldehyde oxidase (
) catalyses the conversion of an aldehyde in the presence of oxygen and water to an acid and hydrogen peroxide. The enzyme is a homodimer, and requires FAD, molybdenum and two 2FE-2S clusters as cofactors. Xanthine dehydrogenase (
) catalyses the hydrogenation of xanthine to urate, and also requires FAD, molybdenum and two 2FE-2S clusters as cofactors. This activity is often found in a bifunctional enzyme with xanthine oxidase (
) activity too. The enzyme can be converted from the dehydrogenase form to the oxidase form irreversibly by proteolysis or reversibly through oxidation of sulphydryl groups.
The aldehyde oxidase and xanthine dehydrogenase, a/b hammerhead domain is an evolutionary conserved protein domain [
,
].
Proteins containing this domain form structural complexes with other known families, such as
and
. The carbon monoxide (CO) dehydrogenase of Oligotropha carboxidovorans is a heterotrimeric complex composed of a apoflavoprotein, a molybdoprotein, and an iron-sulphur protein. It can be dissociated with sodium dodecylsulphate [
]. CO dehydrogenase catalyzes the oxidation of CO according to the following equation []: CO + H2O = CO2 + 2e + 2H+ Subunit S represents the iron-sulphur protein of CO dehydrogenase and is clearly divided into a C- and an N-terminal domain, each binding a [2Fe-2S] cluster [].
The [2Fe-2S] binding domain is found in a range of enzymes including dehydrogenases, oxidases and oxidoreductases.The aldehyde oxido-reductase (Mop) from the sulphate reducing anaerobic Gram-negative bacterium Desulfovibrio gigas is a homodimer of 907 amino acid residues subunits and is a member of the xanthine oxidase family. The protein contains a molybdopterin cofactor (Mo-co) and two different [2Fe-2S] centres. It is folded into four domains of which the first two bind the iron sulphur centres and the last two are involved in Mo-co binding. Mo-co is a molybdenum molybdopterin cytosine dinucleotide. Molybdopterin forms a tricyclic system with the pterin bicycle annealed to a pyran ring. The molybdopterin dinucleotide is deeply buried in the protein. The cis-dithiolene group of the pyran ring binds the molybdenum, which is coordinated by three more (oxygen) ligands [].
Ferredoxins are iron-sulphur proteins that mediate electron transfer in a range of metabolic reactions [
,
]; they fall into several subgroups according to the nature of their iron-sulphur cluster(s). One group,originally found in chloroplast membranes, has been termed 'chloroplast-type' or 'plant-type', and includes ferredoxins
from plants, algae, archaea, rhodobacter and a toluene degrading pseudomonas. Here, the active centre is a2Fe-2S cluster, where the irons are tetrahedrally coordinated by both inorganic sulphurs and sulphurs provided by 4
conserved Cys residues []. In chloroplasts, 2Fe-2S ferredoxins function as electron carriers in thephotosynthetic electron transport chain and as electron donors to various cellular proteins. In
hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers betweenreductase flavoproteins and oxygenase [
].Several oxidoreductases contain redox domains similar to 2Fe-2S ferredoxins, including ferredoxin/ferredoxin
reductase components of several bacterial aromatic di- and monooxygenases, phenol hydroxylase, methane monooxygenase, vanillate demethylase oxidoreductase, phthalate dioxygenase reductase, bacterial fumarate
reductase iron-sulphur protein, eukaryotic succinate dehydrogenase and xanthine dehydrogenase. 3D structures are known for a number of 2Fe-2S ferredoxins [
] and for the ferredoxin reductase/ferredoxin fusion protein phthalate dioxygenase reductase [
]. The fold belongs to the alpha + beta class, with 3 helices and 4 strands forming a barrel-like structure, and an extruded loop containing 3 of the 4 cysteinyl residues of the
iron-sulphur cluster.In the 2Fe-2S ferredoxins, four cysteine residues bind the iron-sulphur cluster. Three of these cysteines are clustered together in the same region of the protein. This sequence cover the three cysteine residues involved in iron-sulphur binding.
This group represents ribosomal RNA assembly protein KRR1, required for 40S ribosome biogenesis. It is involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly in Saccharomyces cerevisiae [
,
]. In Schizosaccharomyces pombe it is known as Mis3 [].
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 L30 is one of the proteins from the large ribosomal subunit. L30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila, slime mould, fungal and mammalian L7 ribosomal proteins. L30 from bacteria are small proteins of about 60 residues. This model describes bacterial, chlorplast and mitochondrial forms of ribosomal protein L30, as well as some yeast mitochondrial L33.
Ribosomal protein L30, ferredoxin-like fold domain
Type:
Domain
Description:
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 L30 is one of the proteins from the large ribosomal subunit. L30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila melanogaster, Dictyostelium discoideum (Slime mold), fungal and mammalian L7 ribosomal proteins. L30 from bacteria are small proteins of about 60 residues, those from archaea are proteins of about 150 residues, and eukaryotic L7 are proteins of about 250 to 270 residues. L30 is missing in some groups of bacteria, such as the CPR group, the PVC group, Cyanobacteria, and some symbionts, which suggests that it is non-essential [,
].This entry represents a domain with a ferredoxin-like fold, with a core structure consisting of core: beta-α-β-α-β. This domain is found in prokaryotic ribosomal protein L30 (short-chain member of the family), as well as in archaeal L30 (L30a) (long-chain member of the family), the later containing an additional C-terminal (sub)domain. It is also found in nucleolar proteins with similarity to large ribosomal subunit L7 proteins. These are constituents of 66S pre-ribosomal particles and play an essential role in processing of precursors to the large ribosomal subunit RNAs [
,
,
].
