| Literature References | 1. RAWLINGS, N.D. AND BARRETT, A.J.
Families of cysteine peptidases.
METHODS ENZYMOL. 244 461-486 (1994).
2. BARRETT, A.J. AND RAWLINGS, N.D.
Families and clans of cysteine peptidases
PERSPECTIVES DRUG DISCOVERY DESIGN 6 1-11 (1996).
3. RAWLINGS, N.D. AND BARRETT, A.J.
Family C24 - Clan PA - 3C endopeptidase
http://www.bi.bbsrc.ac.uk/merops/famcards/c24.htm
4. FEDERHEN, S., HOTTON, C., LEIPE, D. AND SOUSSOV, V.
Calicivirus - NCBI Taxonomy Browser
http://www3.ncbi.nlm.nih.gov/htbin-post/Taxonomy/wgetorg?id=11975&lvl=3
5. WIRBLICH, C., THIEL,H. AND MEYERS, G.
Genetic map of the calicivirus rabbit hemorrhagic diesease virus as detected
from in vitro translation studies.
J.VIROL. 70(11) 7974-7983 (1996).
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| Documentation | Cysteine protease activity is dependent on an active dyad of cysteine and
histidine, the order and spacing of these residues varing in the known
families. Nearly half of all cysteine proteases are found exclusively
in viruses [1]. Cysteine protease families have been grouped into five
clans (designated CA, CB, CC, CD and CE) on the basis of structural and
functional similarity. Families C1, C2 and C10, which belong to the CA clan,
have a Cys/His catalytic diad, and are loosely termed papain-like. Families
in the CB clan have a His/Cys diad, and contain enzymes from RNA viruses
distantly related to chymotrypsin. Enzymes in clan CC are also from RNA
viruses, but have a papain-like Cys/His active site. The remaining two
clans, CD and CE, contain only one family each [2]. Some families have not
yet been asigned to a clan.
Two additional clans (PA and PB) have been identified, these containing a
mixture of serine, cysteine and threonine proteases. Clan PA contains a
catalytically-active serine or cysteine nucleophilic residue as part of the
ordered triad His, Asp, Ser (or Cys). Clan PB contains a serine, cysteine or
threonine active residue at the N-terminus of the mature protease [3].
Caliciviruses are positive-stranded ssRNA viruses that cause gastroenteritis
[4]. The calicivirus genome contains two open reading frames, ORF1 and ORF2.
ORF1 encodes a non-structural polypeptide, which has RNA helicase, cysteine
protease and RNA polymerase activity. The regions of the polyprotein in
which these activities lie are similar to proteins produced by the picorna-
viruses. ORF2 encodes a structural protein [5]. Two different families of
caliciviruses can be distinguished on the basis of sequence similarity,
namely those classified as small round structured viruses (SRSVs) and those
classed as non-SRSVs.
Calicivirus proteases from the non-SRSV group, which are members of the PA
protease clan, constitute family C24 of the cysteine proteases (proteases
from SRSVs belong to the C37 family). As mentioned above, the protease
activity resides within a polyprotein. The enzyme cleaves the polyprotein
at sites N-terminal to itself, liberating the polyprotein helicase.
2CENDOPTASE is a 4-element fingerprint that provides a signature for the
cysteine protease (C24) of non-SRSV caliciviruses. The fingerprint was
derived from an initial alignment of 4 sequences: the motifs were drawn
from conserved regions spanning the full length of the polyprotein protease,
focusing on those regions that characterise members of the C24 family but
distinguish them from the C37 proteases - motif 1 includes the active site
histidine residue; and motif 3 contains the catalytic cysteine. Two
iterations on OWL30.2 were required to reach convergence, at which point
a true set comprising 14 sequences was identified.
An update on SPTR37_9f identified a true set of 12 sequences.
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