The Crystal Structure Of A Penicilloyl-Serine Transferase Of Intermediate Penicillin Sensitivity - The Dd-Transpeptidase Of Streptomyces K15

The serine DD-transpeptidase/penicillin-binding protein of Streptomyces K15
catalyzes peptide bond formation in a way that mimics the penicillin-sensitive
peptide cross-linking reaction involved in bacterial cell wall peptidoglycan
assembly. The Streptomyces K15 enzyme is peculiar in that it can be considered as
an intermediate between classical penicillin-binding proteins, for which
benzylpenicillin is a very efficient inactivator, and the resistant
penicillin-binding proteins that have a low penicillin affinity. With its
moderate penicillin sensitivity, the Streptomyces K15 DD-transpeptidase would be
helpful in the understanding of the structure-activity relationship of this
penicillin-recognizing protein superfamily. The structure of the Streptomyces K15
enzyme has been determined by x-ray crystallography at 2.0-A resolution and
refined to an R-factor of 18.6%. The fold adopted by this 262-amino acid
polypeptide generates a two-domain structure that is close to those of class A
beta-lactamases. However, the Streptomyces K15 enzyme has two particular
structural features. It lacks the amino-terminal alpha-helix found in the other
penicilloyl-serine transferases, and it exhibits, at its surface, an additional
four-stranded beta-sheet. These two characteristics might serve to anchor the
enzyme in the plasma membrane. The overall topology of the catalytic pocket of
the Streptomyces K15 enzyme is also comparable to that of the class A
beta-lactamases, except that the Omega-loop, which bears the essential catalytic
Glu(166) residue in the class A beta-lactamases, is entirely modified. This loop
adopts a conformation similar to those found in the Streptomyces R61
DD-carboxypeptidase and class C beta-lactamases, with no equivalent acidic
residue.