Structural basis for the antibiotic activity of ketolides and azalides.

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Schlunzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A

Structural basis for the antibiotic activity of ketolides and azalides.

Structure. 2003 Mar;11(3):329-38.

PubMed ID

12623020 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Quinupristin	50S ribosomal protein L22	Protein	Escherichia coli O157:H7	Yes	Inhibitor	Details

Polypeptides

Name	UniProt ID
50S ribosomal protein L32	P49228	Details