A 1.2-angstrom snapshot of the final step of bacterial cell wall biosynthesis

The cell wall imparts structural strength and shape to bacteria. It is made up of polymeric glycan chains with peptide branches that are cross-linked to form the cell wall. The cross-linking reaction, catalyzed by transpeptid ases, is the last step in cell wall biosynthesis. These enzymes are members of the family of penicillin-binding proteins, the targets of beta -lactam antibiotics. We report herein the structure of a penicillin-binding protein complexed with a cephalosporin designed to probe the mechanism of the cros s-linking reaction catalyzed by transpeptidases. The 1.2-Angstrom resolutio n x-ray structure of this cephalosporin bound to the active site of the bif unctional serine type D-alanyl-D-alanine carboxypeptidase/transpeptidase (E C 3.4.16.4) from Streptomyces sp. strain R61 reveals how the two peptide st rands from the polymeric substrates are sequestered in the active site of a transpeptidase. The structure of this complex provides a snapshot of the e nzyme and the bound cell wall components poised for the final and critical cross-linking step of cell wall biosynthesis.