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

Tania 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

Fingerprint

Peptidyl Transferases
Peptidoglycan
Amino acids
Cells
Amino Acids
Cell Wall
Antibiotics
Substrates
Escherichia coli
Penicillin-Binding Proteins
Lactams
Amines
Enzymes
Anti-Bacterial Agents
Carrier Proteins

ASJC Scopus subject areas

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

Cite this

Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan. / Lupoli, Tania; Tsukamoto, Hirokazu; Doud, Emma H.; Wang, Tsung Shing Andrew; Walker, Suzanne; Kahne, Daniel.

In: Journal of the American Chemical Society, Vol. 133, No. 28, 20.07.2011, p. 10748-10751.

Research output: Contribution to journalArticle

Lupoli, Tania ; Tsukamoto, Hirokazu ; Doud, Emma H. ; Wang, Tsung Shing Andrew ; Walker, Suzanne ; Kahne, Daniel. / Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 28. pp. 10748-10751.
@article{28ae71af725c4c9b8de891b038786aff,
title = "Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan",
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.",
author = "Tania Lupoli and Hirokazu Tsukamoto and Doud, {Emma H.} and Wang, {Tsung Shing Andrew} and Suzanne Walker and Daniel Kahne",
year = "2011",
month = "7",
day = "20",
doi = "10.1021/ja2040656",
language = "English (US)",
volume = "133",
pages = "10748--10751",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "28",

}

TY - JOUR

T1 - Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan

AU - Lupoli, Tania

AU - Tsukamoto, Hirokazu

AU - Doud, Emma H.

AU - Wang, Tsung Shing Andrew

AU - Walker, Suzanne

AU - Kahne, Daniel

PY - 2011/7/20

Y1 - 2011/7/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79960284952&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960284952&partnerID=8YFLogxK

U2 - 10.1021/ja2040656

DO - 10.1021/ja2040656

M3 - Article

VL - 133

SP - 10748

EP - 10751

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 28

ER -