Protein Domain : Peptidase C30, domain 3, coronavirus IPR043477

Type	Homologous_superfamily
Description	This group of cysteine peptidases correspond to MEROPS peptidase family C30 (clan PA(C)). These peptidases are related to serine endopeptidases of family S1 and are restricted to coronaviruses, where they are involved in viral polyprotein processing during replication [ , , ].This Coronavirus (CoV) domain, peptidase C30, is also known as 3C-like proteinase (3CL-pro), or CoV main protease (M-pro) domain and it is highly conserved among coronaviruses. CoV M-pro is a dimer where each subunit is composed of three domains I, II and III. Domains I and II consist of six-stranded antiparallel beta barrels [ ] and together resemble the architecture of chymotrypsin, and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the centre of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain, a globular cluster of five helices, has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad. In contrast to serine proteinases and other cysteine proteinases, which have a catalytic triad, there is no third catalytic residue present [, , , ]. Many drugs have been developed to inhibit CoV M-pro [, ]. This superfamily represents CoV M-pro domain III, which is reported to be required for dimerisation and regulation [ , ]. Whereas the chymotrypsin-like fold formed by domains I and II is also present in MEROPS family S1 peptidases found in plants, animals, fungi, eubacteria, archaea and viruses, the C-terminal extra helical domain III is unique for the coronavirus 3CL proteases [, ].
Short Name	Peptidase_C30_dom3_CoV