| 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).
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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-S26) 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].
Eukaryotic microsomal signal peptidase is involved in the removal of signal
peptides from secretory proteins as they pass into the endoplasmic reticulum
lumen [1]. The peptidase is more complex than its mitochondrial and
bacterial counterparts, containing a number of subunits, ranging from two
in the chicken oviduct peptidase, to five in the dog pancreas protein [1].
A number of these have been shown to be similar and form the eukaryotic
signal peptidase (S26) family. They share sequence similarity with the
bacterial leader peptidases (family S26A), although activity here is mediated
by a serine/histidine dyad rather than a serine/lysine dyad [1].
SIGNALPTASE is a 2-element fingerprint that provides a signature for the
eukaryotic signal peptidase (S26B) family. The fingerprint was derived from
an inital alignment of 5 sequences: the motifs were drawn from conserved
regions within the putative lumenal domain - motif 1 includes the region
encoded by PROSITE pattern SPASE_I_1 (PS00501), which contains the active
serine; and motif 2 includes the region encoded by PROSITE pattern SPASE_I_3
(PS00760), a conserved region of unknown function (the region surrounding
the proposed active His was not sufficiently well conserved to be used as
a diagnostic motif). Two iterations on OWL29.3 were required to reach
convergence, at which point a true set comprising 7 sequences was identified.
An update on SPTR37_9f identified a true set of 12 sequences.
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