1NWX

COMPLEX OF THE LARGE RIBOSOMAL SUBUNIT FROM DEINOCOCCUS RADIODURANS WITH ABT-773

Summary for 1NWX

• Entry DOI: 10.2210/pdb1nwx/pdb
• Descriptor: 23S RIBOSOMAL RNA, ribosomal protein L13, ribosomal protein L14, ... (32 entities in total)
• Functional Keywords: abt-773, macrolide, ketolide, ribosome, 50s, ribosomal subunit
• Biological source: Deinococcus radiodurans; More
• Total number of polymer chains: 31
• Total formula weight: 1380428.28

Authors

Schluenzen, F.,Harms, J.,Franceschi, F.,Hansen, H.A.S.,Bartels, H.,Zarivach, R.,Yonath, A. (deposition date: 2003-02-07, release date: 2003-03-18, Last modification date: 2023-08-16)

Primary citation

Schlunzen, F.,Harms, J.M.,Franceschi, F.,Hansen, H.A.,Bartels, H.,Zarivach, R.,Yonath, A.
Structural basis for the antibiotic activity of ketolides and azalides.
Structure, 11:329-338, 2003

PubMed 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.

PubMed: 12623020
DOI: 10.1016/S0969-2126(03)00022-4

Experimental method

X-RAY DIFFRACTION (3.5 Å)