{PDOC51537}
{PS51537; NV_3CL_PRO}
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* Norovirus 3C-like protease (NV 3CLpro) domain profile *
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Noroviruses (NVs;  formerly  "Norwalk-like viruses") [E1], which belong to the
Caliciviridae, are   the   major   causative   agents  of  nonbacterial  acute
gastroenteritis in  humans.  The  NV genome, which consists of positive-sense,
single-stranded RNA,  contains three open reading frames (ORFs). The first ORF
produces a  polyprotein  that  is processed by the viral 3C-like protease into
six nonstructural  proteins.  The  six  NV  ORF1  nonstructural  proteins  are
homologous to  picornaviral  nonstructural proteins and are named accordingly:
N-terminal protein, 2C-like nucleoside triphosphatase, 3A-like protein, 3B VPg
(genome-linked viral  protein,  3C-like  protease  (NV  3CLpro), and a 3D RNA-
dependent RNA  polymerase. NV 3CLpros are the key enzymes for ORF1 polyprotein
processing and  also  cleave  the  poly(A)-binding  protein,  causing cellular
translation inhibition.  NV  3CLpros  belong to the chymotrypsin-like protease
family, in  that  they  appear  to  have  chymotrypsin-like folds. Whether the
3CLpro domain  has  a  catalytic dyad of composed of histidine and cysteine or
tryad of histidine, glutamate and cysteine remains controversial [1,2]. The NV
3CLpro domain forms peptidase family C37 [E2].

The NV  3CLpro  domain adopts a serine protease-like fold that consists of two
beta-barrels separated  by  a cleft within which lie the active site catalytic
residues (see  <PDB:1WQS>).  The  N-terminal beta barrel has two alpha-helices
and seven  beta-strands.  The  beta-strands  form a twisted antiparallel beta-
sheet ressembling  an incomplete beta-barrel. The core of the incomplete beta-
barrel contains  hydrophobic  residues.  The  active site histidine residue is
found in  the N-terminal beta-barrel, as well as the glutamate. The C-terminal
six-stranded antiparallel  beta-barrel  contains the active site cysteine. The
catalytic site  formed  is  situated deep within a cleft between the N- and C-
terminal beta-barrels [1,2].

The profile we developed covers the entire NV 3CLpro domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: May 2011 / First entry.

[ 1] Nakamura K., Someya Y., Kumasaka T., Ueno G., Yamamoto M., Sato T.,
     Takeda N., Miyamura T., Tanaka N.
     "A norovirus protease structure provides insights into active and
     substrate binding site integrity."
     J. Virol. 79:13685-13693(2005).
     PubMed=16227288; DOI=10.1128/JVI.79.21.13685-13693.2005
[ 2] Zeitler C.E., Estes M.K., Venkataram Prasad B.V.
     "X-ray crystallographic structure of the Norwalk virus protease at
     1.5-A resolution."
     J. Virol. 80:5050-5058(2006).
     PubMed=16641296; DOI=10.1128/JVI.80.10.5050-5058.2006
[E1] https://viralzone.expasy.org/194?outline=all_by_species
[E2] https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=c37

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