| 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. BAIROCH, A. AND RAWLINGS, N.
Classification of peptidase families and index of peptidase entries in
SWISS-PROT.
http://expasy.hcuge.ch/cgi-bin/lists?peptidas.txt
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| Documentation | Proteolytic enzymes that use serine in their catalytic machinery are
widespread and numerous, being found in viruses, bacteria and eukaryotes
[1]. They encompass a range of peptidase activity, including exopeptidase,
endopeptidase, oligopeptidase and omega-peptidase. More than 20 serine
protease families (denoted S1 - S27) have been identified, which have been
grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural
and functional similarities [1]. Structures from four clans have been
examined (SA, SB, SC and SE): these appear to be unrelated, suggesting at
least four evolutionary origins of serine peptidase, and possibly many more
[1]. Since that examination, structural representations from the other two
clan members (SF, SG) have been determined [3].
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].
Proteins from the chymotrypsin clan (SA) have a conserved GXSG pattern at
the active serine site. The S6 family of the SA clan include IgA-specific
endopeptidases [1,3], which cleave prolyl bonds in the hinge regions of
immunoglobulin A heavy chains. Similar specificity is shown by the unrelated
family of M26 metalloendopeptidases.
IGASERPTASE is a 9-element fingerprint that provides a signature for the
IgA-specific endopeptidase (S6) family of serine peptidases. The fingerprint
was derived from an initial alignment of 8 sequences: the motifs were
drawn from conserved regions spanning virtually the full alignment length -
motif 2 includes the catalytic Asp; and motif 3 encodes the catalytically
active Ser. Two iterations on OWL30.1 were required to reach convergence,
at which point a true set comprising 18 sequences was identified. Numerous
partial matches were also found, all of which are fragments: B41500 matches
motifs 1-3; and 16 sequences match motifs 2 and 3 only.
An update on SPTR37_9f identified a true set of 9 sequences, and 7
partial matches.
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