Structural basis for the antibacterial activity of the 12-membered-ring mono-sugar macrolide methymycin

• Authors: T. Auerbach , I. Mermershtain , A. Bashan , C. Davidovich , H. Rozenberg , D.H. Sherman , A. Yonath
• Languages of publication: EN

Abstracts

EN

The crystal structure of the complex of the large ribosomal subunit of the pathogen model Deinococcus radiodurans with the macrolide antibiotic methymycin, bearing a 12 membered macrolactone ring macrolide that contains a single amino sugar, shows that methymycin binds to the peptidyl transferase center (PTC) rather than to the high affinity macrolide binding pocket at the upper end of the ribosomal exit tunnel. This unexpected binding mode result in fairly efficient blockage of the 3'end of the A-site tRNA location, thus indicating the superiority of spatial-functional considerations over the formation of the typical high affinity macrolide interactions that due to the small size of methymycin could have led to incomplete blockage of the exit tunnel. Its binding involves rearrangements of several PTC nucleotides, some of which shown previously to be flexible. Comparisons between the binding modes of methymycin and other antibiotics are presented and discussed.

Keywords

EN

ANTIBIOTIC; CRYSTALLOGRAPHY; MACROLIDE; METHYMYCIN; RIBOSOME; X-RAY

Discipline

• BIOTECHNOLOGY: BIOTECHNOLOGY

• Publisher: Committee of Biotechnology, Polish Academy of Sciences
• Journal: Biotechnologia
• Year: 2009
• Issue: 1
• Pages: 24-35

Contributors

author

T. Auerbach

author

I. Mermershtain

author

A. Bashan

author

C. Davidovich

author

H. Rozenberg

author

D.H. Sherman

author

A. Yonath

• Document Type: REVIEW
• Publication order reference: Ada Yonath, Life Sciences Institute and Departments of Medicinal Chemistry, Chemistry, Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan 48109