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Structural Insight into the Transglycosylation Step of Bacterial Cell-Wall Biosynthesis
Andrew L. Lovering,Liza H. de Castro,Daniel Lim,Natalie C. J. Strynadka*
Peptidoglycan glycosyltransferases (GTs) catalyze the polymerizationstep of cell-wall biosynthesis, are membrane-bound, and arehighly conserved across all bacteria. Long considered the "holygrail" of antibiotic research, they represent an essential andeasily accessible drug target for antibiotic-resistant bacteria,including methicillin-resistant Staphylococcus aureus. We havedetermined the 2.8 angstrom structure of a bifunctional cell-wallcross-linking enzyme, including its transpeptidase and GT domains,both unliganded and complexed with the substrate analog moenomycin.The peptidoglycan GTs adopt a fold distinct from those of otherGT classes. The structures give insight into critical featuresof the catalytic mechanism and key interactions required forenzyme inhibition.
Department of Biochemistry and Molecular Biology, and Center for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, Canada.
* To whom correspondence should be addressed. E-mail: natalie{at}byron.biochem.ubc.ca
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[DOI: 10.1126/science.1140374] |Summary »|Full Text »|PDF »
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