@article{a326e4834ce141baa1e7a64982cafd81,
title = "Structural basis for the antibiotic activity of ketolides and azalides",
abstract = "The azalide azithromycin and the ketolide ABT-773, which were derived by chemical modifications of erythromycin, exhibit elevated activity against a number of penicillin- and macrolide-resistant pathogenic bacteria. Analysis of the crystal structures of the large ribosomal subunit from Deinococcus radiodurans complexed with azithromycin or ABT-773 indicates that, despite differences in the number and nature of their contacts with the ribosome, both compounds exert their antimicrobial activity by blocking the protein exit tunnel. In contrast to all macrolides studied so far, two molecules of azithromycin bind simultaneously to the tunnel. The additional molecule also interacts with two proteins, L4 and L22, implicated in macrolide resistance. These studies illuminated and rationalized the enhanced activity of the drugs against specific macrolide-resistant bacteria.",
keywords = "Antibiotics, Azalides, Azithromycin, Ketolides, Peptidyl transferase center, Ribosome",
author = "Frank Schl{\"u}nzen and Harms, {J{\"o}rg M.} and Francois Franceschi and Hansen, {Harly A.S.} and Heike Bartels and Raz Zarivach and Ada Yonath",
note = "Funding Information: We thank R. Albrecht, A. Bashan, W.S. Bennett, R. Berisio, C. Glotz, C. Liebe, C. Stamer, and A. Wolff for their contributions to different stages of these studies. We would like to acknowledge Abbott's and Pliva's generous gifts of the antimicrobial agents and their structures. These studies could not be performed without the excellent support by the staff of the synchrotron radiation facilities ID14-2/4 at ESRF, namely, E. Mitchell, J. McCarthy, and R. Ravelli, and the staff at the SBC beamline ID-19, namely, R. Alkire and S. Ginell. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Biological and Environmental Research, under contract number W-31-109-ENG-38. Support was provided by the Max-Planck-Society, the U.S. National Institutes of Health (GM34360), the German Ministry for Science and Education (BMBF Grant 05-641EA), and the Kimmelman Center for Macromolecular Assembly at the Weizmann Institute. A.Y. holds the Helen and Martin S. Kimmel Professorial Chair. ",
year = "2003",
month = mar,
day = "1",
doi = "10.1016/S0969-2126(03)00022-4",
language = "English",
volume = "11",
pages = "329--338",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "3",
}