Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis

Department of Biochemistry and Molecular Biology, and Center for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, Canada.
Science (Impact Factor: 31.48). 04/2007; 315(5817):1402-5. DOI: 10.1126/science.1136611
Source: PubMed

ABSTRACT Peptidoglycan glycosyltransferases (GTs) catalyze the polymerization step of cell-wall biosynthesis, are membrane-bound, and are highly conserved across all bacteria. Long considered the "holy grail" of antibiotic research, they represent an essential and easily accessible drug target for antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus. We have determined the 2.8 angstrom structure of a bifunctional cell-wall cross-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 other GT classes. The structures give insight into critical features of the catalytic mechanism and key interactions required for enzyme inhibition.

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