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).
Proteolytic enzymes that exploit serine in their catalytic activity are
ubiquitous, being found in viruses, bacteria and eukaryotes . 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 . 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 .
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 . The geometric orientations of
the catalytic residues are similar between families, despite different
protein folds . 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].
The lexA protein represses around 20 genes of the cellular SOS response to
DNA damage in E.coli . Damage to cellular DNA results in inactivation of
lexA, allowing transcription of the genes involved in DNA repair . In
E.coli, this derepression of the DNA repair system is effected by the recA
protein, which binds to lexA upon interaction with single-stranded
DNA . This results in inactivation of lexA by proteolytic cleavage,
disrupting the DNA-binding capabilities of lexA . Although initially
thought to be mediated by recA, it has been found that the cleavage of lexA
is an autolytic event catalysed by the presence of recA .
The lexA protein consists of around 200 amino acids, of which the first 90
form the DNA-binding domain . The remaining residues form the protease
domain, Ser-119 and Lys-156 being the active residues.
LEXASERPTASE is a 3-element fingerprint that provides a signature for the
protease domain of the lexA repressor and related proteins. The fingerprint
was derived from an initial alignment of 8 sequences: the motifs were drawn
from conserved regions spanning the C-terminal half of the alignment in the
vicinity of the active site - motif 1 contains the catalytic serine,
and motif 3 the catalytic lysine. Two iterations on OWL29.3 were
required to reach convergence, at which point a true set comprising 17
sequences was identified. A single partial match was also found, RNU77699,
a fragment that shows a high degree of similarity to the first 2 motifs.
An update on SPTR37_9f identified a true set of 26 sequences.