The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity.

Bolam, D.N., Roberts, S., Proctor, M.R., Turkenburg, J.P., Dodson, E.J., Martinez-Fleites, C., Yang, M., Davis, B.G., Davies, G.J. and Gilbert, H.J. (2007) The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity. Proceedings of the National Academy of Sciences of the USA, 104 (13). pp. 5336-5341. 10.1073/pnas.0607897104 .

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DOI: 10.1073/pnas.0607897104

Abstract

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.

Item Type:Article
Additional Information:Full text available in print and electronically from the School of Pharmacy Library.
Uncontrolled Keywords:enzymology; glycobiology; erythromycin; streptomyces; glycoside
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:916
Journal or Publication Title:Proceedings of the National Academy of Sciences of the USA
Deposited By:Library Staff
Deposited On:14 May 2008 16:16
Last Modified:07 Oct 2011 15:49

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