A 1.2-A 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 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.
Lee
W
W
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269-3125, USA.
McDonough
M A
MA
Kotra
L
L
Li
Z H
ZH
Silvaggi
N R
NR
Takeda
Y
Y
Kelly
J A
JA
Mobashery
S
S
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
D002511:Cephalosporins; D002268:Carboxypeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase