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
4. GHUYSEN J-M.
Serine beta-lactamases and penicillin-binding proteins.
ANNU.REV.MICROBIOL. 45 37-67 (1991).
Proteolytic enzymes that use serine in their catalytic machinery are
widespread and numerous, being found in viruses, bacteria and eukaryotes
. 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 . 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
. Since that examination, structural representations from the other two
clan members (SF, SG) have been determined .
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].
D-Ala-D-Ala carboxypeptidase (clan SE) is involved in the metabolism of
cell components ; it is synthesised with a leader peptide to target it
to the cell membrane . After cleavage of the leader peptide, the enzyme
is retained in the membrane by a C-terminal anchor . There are three
families of serine-type D-Ala-D-Ala peptidase (designated S11, S12 and S13),
which are also known as low molecular weight penicillin-binding proteins .
Family S13 comprises D-Ala-D-Ala peptidases that have sufficient sequence
similarity around their active sites to assume a distant evolutionary
relationship to other clan members; members of the S13 family also bind
penicilin and have D-amino-peptidase activity. Proteases of family S11 have
exclusive D-Ala-D-Ala peptidase activity, while some members of S12 are
C beta-lactamases .
DADACBPTASE3 is a 5-element fingerprint that provides a signature for the
D-Ala-D-Ala carboxypeptidase 1 (S13) family of serine proteases. The
fingerprint was derived from an initial alignment of 7 sequences: the
motifs were drawn from conserved regions surrounding the active site -
motif 1 contains the catalytic Ser, and Lys residues; motifs 2 and 3 include
Ser and Asp residues, both of which have been implicated in the catalytic
mechanism of the related beta-lactamase A. A single iteration on OWL30.1
was required to reach convergence, no further sequences being identified
beyond the starting set.
An update on SPTR37_9f identified a true set of 9 sequences, and 1