Structural Insight into the Transglycosylation Step of Bacterial Cell-Wall Biosynthesis
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.
- Publication:
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Science
- Pub Date:
- March 2007
- DOI:
- 10.1126/science.1136611
- Bibcode:
- 2007Sci...315.1402L
- Keywords:
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- BIOCHEM