PROSITE documentation PDOC51442Coronavirus main protease (M-pro) domain profile
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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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Anand K. Palm G.J. Mesters J.R. Siddell S.G. Ziebuhr J. Hilgenfeld R. |
| Title | Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain. | |
| Source | EMBO J. 21:3213-3224(2002). | |
| PubMed ID | 12093723 | |
| DOI | 10.1093/emboj/cdf327 |
| 2 | Authors | Anand K. Ziebuhr J. Wadhwani P. Mesters J.R. Hilgenfeld R. |
| Title | Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. | |
| Source | Science 300:1763-1767(2003). | |
| PubMed ID | 12746549 | |
| DOI | 10.1126/science.1085658 |
| 3 | Authors | Xue 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. |
| Title | Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design. | |
| Source | J. Virol. 82:2515-2527(2008). | |
| PubMed ID | 18094151 | |
| DOI | 10.1128/JVI.02114-07 |
| 4 | Authors | Zhao Q. Li S. Xue F. Zou Y. Chen C. Bartlam M. Rao Z. |
| Title | Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1. | |
| Source | J. Virol. 82:8647-8655(2008). | |
| PubMed ID | 18562531 | |
| DOI | 10.1128/JVI.00298-08 |
| E1 | Title | https://viralzone.expasy.org/30?outline=all_by_protein |
| E2 | Title | https://www.ebi.ac.uk/merops/cgi-bin/merops.cgi?id=C30 |
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