Our deepest condolences go out to his family and friends, and to all those who had the privilege of working with him. Rest in peace, Amos. Your work will live on long after you are gone.
PROSITE documentation PDOC51442Coronavirus main protease (M-pro) domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC51442
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/famsum?family=C30 |
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