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PROSITE documentation PDOC51442 [for PROSITE entry PS51442]

Coronavirus main protease (M-pro) domain profile





Description

Coronaviruses (CoVs) are positive-stranded RNA viruses that can infect humans and multiple species of animals, causing a wide spectrum of diseases [E1]. The CoV replicase gene encodes two overlapping polyproteins, termed pp1a and pp1ab, which mediate viral replication and transcription. The maturation of CoVs involves a highly complex cascade of proteolytic processing events on the polyproteins to control viral gene expression and replication. Most maturation cleavage events within the precursor polyprotein are mediated by a viral cysteine proteinase which is called the 'main proteinase' (M-pro) or, alternatively, the '3C-like proteinase' (3CL-pro). The ~300-residue mature form of the M-pro is released from pp1a and pp1ab by autoproteolytic cleavage and employs conserved cysteine and histidine residues in the catalytic site [1,2,3,4]. It belongs to peptidase family C30 [E2].

The CoV M-pro comprises three domains (see <PDB:1LVO>). Domains I and II are six-stranded antiparallel β barrels and together ressemble 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 center 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 [1,2,3,4].

The profile we developed covers the entire M-pro domain.

Last update:

March 2009 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

M_PRO, PS51442; Coronavirus main protease (M-pro) domain profile  (MATRIX)


References

1AuthorsAnand K. Palm G.J. Mesters J.R. Siddell S.G. Ziebuhr J. Hilgenfeld R.
TitleStructure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain.
SourceEMBO J. 21:3213-3224(2002).
PubMed ID12093723
DOI10.1093/emboj/cdf327

2AuthorsAnand K. Ziebuhr J. Wadhwani P. Mesters J.R. Hilgenfeld R.
TitleCoronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs.
SourceScience 300:1763-1767(2003).
PubMed ID12746549
DOI10.1126/science.1085658

3AuthorsXue X. Yu H. Yang H. Xue F. Wu Z. Shen W. Li J. Zhou Z. Ding Y. Zhao Q. Zhang X.C. Liao M. Bartlam M. Rao Z.
TitleStructures of two coronavirus main proteases: implications for substrate binding and antiviral drug design.
SourceJ. Virol. 82:2515-2527(2008).
PubMed ID18094151
DOI10.1128/JVI.02114-07

4AuthorsZhao Q. Li S. Xue F. Zou Y. Chen C. Bartlam M. Rao Z.
TitleStructure of the main protease from a global infectious human coronavirus, HCoV-HKU1.
SourceJ. Virol. 82:8647-8655(2008).
PubMed ID18562531
DOI10.1128/JVI.00298-08

E1Titlehttps://viralzone.expasy.org/30?outline=all_by_protein

E2Titlehttps://www.ebi.ac.uk/merops/cgi-bin/merops.cgi?id=C30



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