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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Crystallography, X-Ray
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Enzyme Inhibitors / chemistry
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Escherichia coli / enzymology*
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Escherichia coli Proteins / antagonists & inhibitors*
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Escherichia coli Proteins / chemistry*
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Molecular Sequence Data
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Oligosaccharides / chemistry
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Penicillin-Binding Proteins / antagonists & inhibitors*
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Penicillin-Binding Proteins / chemistry*
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Peptidoglycan Glycosyltransferase / antagonists & inhibitors*
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Peptidoglycan Glycosyltransferase / chemistry*
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Protein Conformation
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Serine-Type D-Ala-D-Ala Carboxypeptidase / antagonists & inhibitors*
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Serine-Type D-Ala-D-Ala Carboxypeptidase / chemistry*
Substances
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Enzyme Inhibitors
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Escherichia coli Proteins
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Oligosaccharides
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Penicillin-Binding Proteins
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Peptidoglycan Glycosyltransferase
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penicillin-binding protein 1B, E coli
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Serine-Type D-Ala-D-Ala Carboxypeptidase
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moenomycin