| Literature References | 1. RAWLINGS, N.D. AND BARRETT, A.J.
Families of serine peptidases.
METHODS ENZYMOL. 244 19-61 (1994).
2. RAWLINGS, N.D AND BARRETT, A.J.
Evolutionary families of peptidases.
BIOCHEM.J. 290 205-218 (1993).
3. WISKERCHEN, M. AND COLLETT, M.S.
Pestivirus gene expression: protein p80 of bovine viral diarrhoea virus is a
proteinase involved in polyprotein processing.
VIROLOGY 184 341-350 (1991).
4. BAZAN, J.F. AND FLETTERICK, R.J.
Detection of a trypsin-like serine protease domain in flaviviruses and
pestiviruses.
VIROLOGY 171 637-639 (1989).
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| Documentation | Proteolytic enzymes that exploit serine in their catalytic activity are
ubiquitous, being found in viruses, bacteria and eukaryotes [1]. They
include a wide range of peptidase activity, including exopeptidase, endo-
peptidase, oligopeptidase and omega-peptidase activity. Over 20 families
(denoted S1 - S27) of serine protease have been identified, these being
grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural
similarity and other functional evidence [1]. Structures are known for four
of the clans (SA, SB, SC and SE): these appear to be totally unrelated,
suggesting at least four evolutionary origins of serine peptidases and
possibly many more [1].
Notwithstanding their different evolutionary origins, there are similarities
in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin
and carboxypeptidase C clans have a catalytic triad of serine, aspartate and
histidine in common: serine acts as a nucleophile, aspartate as an
electrophile, and histidine as a base [1]. The geometric orientations of
the catalytic residues are similar between families, despite different
protein folds [1]. The linear arrangements of the catalytic residues
commonly reflect clan relationships. For example the catalytic triad in
the chymotrypsin clan (SA) is ordered HDS, but is ordered DHS in the
subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [1,2].
Cattle diarrhoea virus and hog cholera virus belong to the pestiviruses,
single-stranded RNA viruses whose genomes encode one large polyprotein [1].
The p80 endopeptidase resides towards the middle of the polyprotein and is
responsible for processing all non-structural pestivirus proteins [1,3].
The p80 enzyme is similar to other proteases in the SA clan and is predicted
to have a fold similar to that of chymotrypsin [1,4]. An HDS catalytic triad
has been identified [4].
CDVENDOPTASE is a 3-element fingerprint that provides a signature for the
cattle virus p80 endopeptidase and related peptides (family S31). The
fingerprint was derived from an initial alignment of 4 sequences: the motifs
were drawn from conserved regions around the active site of the p80 protease
domain, the central residue of each motif being the active His, Asp and Ser
respectively. Two iterations on OWL29.3 were required to reach convergence,
at which point a true set comprising 30 sequences was identified. Three
partial matches were also found, all of which are fragments that lack one
of the 3 motifs.
An update on SPTR37_9f identified a true set of 24 sequences.
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