Lookup NU author(s): Dr David Bolam,
Dr Mark Proctor,
Professor Harry Gilbert
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Glycosylation of macrolide antibiotics confers host cell immunity from endogenous and exogenous agents. The Streptomyces antibioticus glycosyltransferases, OleI and OleD, glycosylate and inactivate oleandomycin and diverse macrolides including erythromycin, respectively. The structure of these enzyme-ligand complexes, in tandem with kinetic analysis of site-directed variants, provide insight into the interaction of macrolides with their synthetic apparatus. Erythromycin binds to OleD and the 23S RNA of its target ribosome in the same conformation and, although the antibiotic contains a large number of polar groups, its interaction with these macromolecules is primarily through hydrophobic contacts. Erythromycin and oleandomycin, when bound to OleD and OleI, respectively, adopt different conformations, reflecting a subtle effect on sugar positioning by virtue of a single change in the macrolide backbone. The data reported here provide structural insight into the mechanism of resistance to both endogenous and exogenous antibiotics, and will provide a platform for the future redesign of these catalysts for antibiotic remodelling. © 2007 by The National Academy of Sciences of the USA.
Author(s): Bolam DN, Roberts S, Proctor MR, Turkenburg J, Dodson E, Martinez-Fleites C, Yang M, Davis B, Davies G, Gilbert HJ
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
PubMed id: 17376874
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