{PDOC51442}
{PS51442; M_PRO}
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* Coronavirus main protease (M-pro) domain profile *
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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 beta 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: March 2009 / First entry.

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

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