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Transpeptidase-mediated incorporation of D-amino acids into bacterial peptidoglycan.

ABSTRACT: The ?-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse D-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical D-amino acids can be introduced into the bacterial cell wall.

SUBMITTER: Lupoli TJ

PROVIDER: S-EPMC3172152 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Transpeptidase-mediated incorporation of D-amino acids into bacterial peptidoglycan.

Lupoli Tania J TJ Tsukamoto Hirokazu H Doud Emma H EH Wang Tsung-Shing Andrew TS Walker Suzanne S Kahne Daniel D

Journal of the American Chemical Society 20110627 28

The β-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual step ...[more]

PMID: 21682301

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