title: A 1.2-A snapshot of the final step of bacterial cell wall biosynthesis.
abstract: 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 transpeptidases, 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 cross-linking reaction catalyzed by transpeptidases. The 1.2-A resolution x-ray structure of this cephalosporin bound to the active site of the bifunctional serine type D-alanyl-D-alanine carboxypeptidase/transpeptidase (EC ) from Streptomyces sp. strain R61 reveals how the two peptide strands from the polymeric substrates are sequestered in the active site of a transpeptidase. The structure of this complex provides a snapshot of the enzyme and the bound cell wall components poised for the final and critical cross-linking step of cell wall biosynthesis.
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269-3125, USA.
authors.forename: W
authors.initials: W
authors.lastname: Lee
authors.forename: M A
authors.initials: MA
authors.lastname: McDonough
authors.forename: L
authors.initials: L
authors.lastname: Kotra
authors.forename: Z H
authors.initials: ZH
authors.lastname: Li
authors.forename: N R
authors.initials: NR
authors.lastname: Silvaggi
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: J A
authors.initials: JA
authors.lastname: Kelly
authors.forename: S
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D000215:Acylation; D002268:Carboxypeptidases / Q000737:chemistry*; D002473:Cell Wall; D002511:Cephalosporins / Q000138:chemical synthesis / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013302:Streptomyces / Q000201:enzymology
chemical_list: D002511:Cephalosporins; D002268:Carboxypeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase