Peptidase family C16 (EC 3.4.22.-) contains the coronaviruses cysteine
endopeptidases involved in viral polyprotein processing [E1]. All
coronaviruses encodes between one and two accessory cysteine proteinases that
recognize and process one or two sites in the amino-terminal half of the
replicase polyprotein during assembly of the viral replication complex. MHV,
HCoV and TGEV encode two accesssory proteinases, called coronavirus
papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO). IBV and SARS encodes
only one called PL-PRO . Coronaviruses papain-like proteinases 1 and 2 have
restricted specificities, cleaving respectively two and one bond(s)in the
polyprotein. This restricted activity may be due to extended specificity
sites: Arg or Lys at the cleavage site position P5 are required for PL1-PRO
, and Phe at the cleavage site position P6 is required for PL2-PRO .
PL1-PRO releases p28 and p65 from the N-terminus of the polyprotein; PL2-PRO
cleaves between p210 and p150.
The peptidase family C16 domain is about 260 amino acids in length. This
domain is predicted to have an α-β structural organisation known as the
papain-like fold. It consists of three α-helices and three strands of
antiparallel β-sheet . This domain has a catalytic dyad consisting of a
Cys and a downstream His [1,2,4]. The nucleophilic Cys occurs in the motif
Asn-Cys-Xaa-Yaa in which Xaa is an aromatic, hydrophobic residue and Yaa is an
aliphatic hydrophobic amino acid. There is little conservation around the
general base His. This peptidase domain also contains Cys residues involved in
the formation of a zinc-binding finger which connects the left and right hand
domains of a papain-like fold, and may be involved in substrate binding or
control the movement of the catalytic domain .
Some proteins known to contain a peptidase C16 domain are listed below:
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