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Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli.

ABSTRACT: Drug-resistant bacteria have caused serious medical problems in recent years, and the need for new antibacterial agents is undisputed. Transglycosylase, a multidomain membrane protein essential for cell wall synthesis, is an excellent target for the development of new antibiotics. Here, we determined the X-ray crystal structure of the bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from Escherichia coli in complex with its inhibitor moenomycin to 2.16-A resolution. In addition to the transglycosylase and transpeptidase domains, our structure provides a complete visualization of this important antibacterial target, and reveals a domain for protein-protein interaction and a transmembrane helix domain essential for substrate binding, enzymatic activity, and membrane orientation.

SUBMITTER: Sung MT

PROVIDER: S-EPMC2689995 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli.

Sung Ming-Ta MT Lai Yen-Ting YT Huang Chia-Ying CY Chou Lien-Yang LY Shih Hao-Wei HW Cheng Wei-Chieh WC Wong Chi-Huey CH Ma Che C

Proceedings of the National Academy of Sciences of the United States of America 20090519 22

Drug-resistant bacteria have caused serious medical problems in recent years, and the need for new antibacterial agents is undisputed. Transglycosylase, a multidomain membrane protein essential for cell wall synthesis, is an excellent target for the development of new antibiotics. Here, we determined the X-ray crystal structure of the bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from Escherichia coli in complex with its inhibitor moenomycin to 2.16-A resolution. In additio ...[more]

PMID: 19458048

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