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. GHUYSEN J-M.
Serine beta-lactamases and penicillin-binding proteins.
ANNU.REV.MICROBIOL. 45 37-67 (1991).
4. PALOMEQUE-MESSIA, ENGELBERT, S., LEYH-BOUILLE, M., NGUYEN-DISTECHE, M.,
DUEZ, C., HOUBA, S., DIDEBERG, O., VAN BEEUMEN, J. AND GHUYSEN, J-M.
Amino acid sequence of the penicillin-binding protein/DD-peptidase of
Streptomyces K15. Predicted secondary structures of the low Mr penicillin-
binding proteins of class A.
BIOCHEM.J. 279 223-230 (1991).
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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 - 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 [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].
Bacterial cell walls are complex structures containing amino acids and
amino sugars, with alternating chains of N-acetylglucosamine and N-acetyl-
muramic acid units linked by short peptides [1]: the link peptide in E.coli
is L-alanyl-D-isoglutamyl-L-meso-diaminopimelyl-D-alanine [1]. The chains
are usually cross-linked between the carboxyl of D-alanine and the free
amino group of diaminopimelate [1]. During the synthesis of peptidoglycan,
the precursor has the described tetramer sequence with an added C-terminal
D-alanine [1].
D-Ala-D-Ala carboxypeptidase is involved in the metabolism of cell
components [3]; it is synthesised with a leader peptide to target it to
the cell membrane [1]. After cleavage of the leader peptide, the enzyme is
retained in the membrane by a C-terminal anchor [1]. There are three
families of serine-type D-Ala-D-Ala peptidase, which are also known as
low molecular weight penicillin-binding proteins [1].
Family S11 contains only D-Ala-D-Ala peptidases, unlike families S12 and S13,
which contain other enzymes, such as class C beta-lactamases and D-amino-
peptidases [1]. Although these enzymes are serine proteases, some members
of family S11 are partially inhibited by thiol-blocking agents [4].
DADACBPTASE1 is a 3-element fingerprint that provides a signature for the
D-Ala-D-Ala carboxypeptidase 1 (S11) family of serine proteases. The
fingerprint was derived from an initial alignment of 8 sequences: the motifs
were largely drawn from conserved regions surrounding the active site -
motif 1 contains the catalytic Ser and Lys residues; and motif 2 includes
a Ser residue that has been implicated in catalysis in the related protein
beta-lactamase A. Three iterations on OWL29.2 were required to reach
convergence, at which point a true set comprising 21 sequences was
identified. A single partial match was also found, CPDACF, a fragment
lacking the portion of sequence bearing motif 1.
An update on SPTR37_9f identified a true set of 22 sequences, and 1
partial match.
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