Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan

Tania J. Lupoli, Hirokazu Tsukamoto, Emma H. Doud, Tsung Shing Andrew Wang, Suzanne Walker, Daniel Kahne

Research output: Contribution to journalArticle

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)10748-10751
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number28
DOIs
StatePublished - Jul 20 2011

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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