Crystal Structure of the Oxazolidinone Antibiotic Linezolid Bound to the 50S Ribosomal Subunit

Journal Article · Mon Dec 31 23:00:00 EST 2007 · Journal of Medicinal Chemistry

DOI:https://doi.org/10.1021/jm800379d· OSTI ID:959537

Ippolito, J; Kanyo, Z; Wang, D; Franceschi, F; Moore, P; Steitz, T; Duffy, E

The oxazolidinone antibacterials target the 50S subunit of prokaryotic ribosomes. To gain insight into their mechanism of action, the crystal structure of the canonical oxazolidinone, linezolid, has been determined bound to the Haloarcula marismortui 50S subunit. Linezolid binds the 50S A-site, near the catalytic center, which suggests that inhibition involves competition with incoming A-site substrates. These results provide a structural basis for the discovery of improved oxazolidinones active against emerging drug-resistant clinical strains.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959537
• Report Number(s): BNL--82523-2009-JA
• Journal Information: Journal of Medicinal Chemistry, Journal Name: Journal of Medicinal Chemistry Journal Issue: 12 Vol. 51; ISSN JMCMAR; ISSN 0022-2623
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ANTIBIOTICS
CRYSTAL STRUCTURE
RIBOSOMES
STRAINS
SUBSTRATES
TARGETS
national synchrotron light source