{PDOC51874}
{PS51874; PCV_3C_PRO}
{BEGIN}
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* Picornavirales 3C/3C-like protease domain profile *
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Viruses in the order Picornavirales infect different vertebrate, invertebrate,
and plant  hosts and are responsible for a variety of human, animal, and plant
diseases. Viruses  in  this  order  have a single-stranded, positive sense RNA
(+ssRNA) genome  that  generally  translates  a  large precusrsor polyprotein.
After translation,  the viral precursor polyprotein is proteolytically cleaved
to generate  mature  functional  viral  proteins.  This  maturation process is
usually mediated  by  (more  than  one)  proteases,  and  a 3C (for the family
Picornaviridae) or 3C-like (3CL) protease (for other families) plays a central
role in  the  cleavage  of the viral precursor polyprotein. In addition to its
key role  in processing the polyprotein, 3C/3C-like protease is able to cleave
a number  of  host  proteins  to  remodel  the  cellular environment for virus
reproduction [1,2,3,4,5,6].  The  Picornavirales  3C/3C-like  protease  domain
forms the peptidase family C3 (picornain family) of clan PA [E1].

The 3C/3CL  protease  domain  adopts  a chymotrypsin-like fold with a cysteine
nucleophile in  place  of a commonly found serine. Accordingly, 3C and 3C-like
proteases partially  tolerate  a  replacement  of  the catalytic cysteine by a
serine, and  vice-versa,  suggesting  that  the cysteine and serine perform an
analogous catalytic  function.  The catalytic triad is made of a histidine, an
aspartate/glutamate and  the  conserved cysteine in this sequential order. The
3C/3CL protease  domain  folds  into  two  antiparallel  beta barrels that are
linked by  a  loop  with a short alpha-helix in its middle, and flanked by two
other alpha-helices  at the N- and C-termini (see <PDB:3Q3X>). The two barrels
are topologically  equivalent  and are formed by six antiparallel beta strands
with the first four organized into a Greek key motif. The active-site residues
are located  in  the  cleft  between the two barrels with the nucleophilic Cys
from the  C-terminal  barrel and the general acid base His-Glu/Asp from the N-
terminal barrel [1,2,4].

The profile we developed covers the entire 3C/3C-like protease domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2019 / First entry.

[ 1] Birtley J.R., Knox S.R., Jaulent A.M., Brick P., Leatherbarrow R.J.,
     Curry S.
     "Crystal structure of foot-and-mouth disease virus 3C protease. New
     insights into  catalytic mechanism and cleavage specificity."
     J. Biol. Chem. 280:11520-11527(2005).
     PubMed=15654079; DOI=10.1074/jbc.M413254200
[ 2] Le Gall O., Christian P., Fauquet C.M., King A.M.Q., Knowles N.J.,
     Nakashima N., Stanway G., Gorbalenya A.E.
     "Picornavirales, a proposed order of positive-sense single-stranded
     RNA viruses with a pseudo-T = 3 virion architecture."
     Arch. Virol. 153:715-727(2008).
     PubMed=18293057; DOI=10.1007/s00705-008-0041-x
[ 3] Lee C.-C., Kuo C.-J., Ko T.-P., Hsu M.-F., Tsui Y.-C., Chang S.-C.,
     Yang S., Chen S.-J., Chen H.-C., Hsu M.-C., Shih S.-R., Liang P.-H.,
     Wang A.H.-J.
     "Structural basis of inhibition specificities of 3C and 3C-like
     proteases by zinc-coordinating and peptidomimetic compounds."
     J. Biol. Chem. 284:7646-7655(2009).
     PubMed=19144641; DOI=10.1074/jbc.M807947200
[ 4] Costenaro L., Kaczmarska Z., Arnan C., Janowski R., Coutard B.,
     Sola M., Gorbalenya A.E., Norder H., Canard B., Coll M.
     "Structural basis for antiviral inhibition of the main protease, 3C,
     from human enterovirus 93."
     J. Virol. 85:10764-10773(2011).
     PubMed=21835784; DOI=10.1128/JVI.05062-11
[ 5] Lu G., Qi J., Chen Z., Xu X., Gao F., Lin D., Qian W., Liu H.,
     Jiang H., Yan J., Gao G.F.
     "Enterovirus 71 and coxsackievirus A16 3C proteases: binding to
     rupintrivir and their substrates and anti-hand, foot, and mouth
     disease virus drug design."
     J. Virol. 85:10319-10331(2011).
     PubMed=21795339; DOI=10.1128/JVI.00787-11
[ 6] Ye S., Xia H., Dong C., Cheng Z., Xia X., Zhang J., Zhou X., Hu Y.
     "Identification and characterization of Iflavirus 3C-like protease
     processing activities."
     Virology 428:136-145(2012).
     PubMed=22534091; DOI=10.1016/j.virol.2012.04.002
[E1] https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=C3

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