U2504 Determines the Species Specificity of the A-Site Cleft Antibiotics: The Structures of Tiamulin, Homoharringtonine, and Bruceantin Bound to the Ribosome

Journal Article · Tue Jun 30 04:00:00 EDT 2009 · J. Mol. Biol.

DOI:https://doi.org/10.1016/j.jmb.2009.04.005· OSTI ID:1005671

Gürel, Güliz; Blaha, Gregor; Moore, Peter B; Steitz, Thomas A; Yale,

Structures have been obtained for the complexes that tiamulin, homoharringtonine, and bruceantin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 {angstrom}. They show that all these inhibitors block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the Asite cleft in the peptidyl-transferase center, which is universally conserved. In addition, these structures support the hypothesis that the species specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (Escherichia coli). In the ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005671
• Journal Information: J. Mol. Biol., Journal Name: J. Mol. Biol. Journal Issue: (1) ; 05, 2009 Vol. 389; ISSN JMOBAK; ISSN 0022-2836
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
AMINO ACIDS
ANTIBIOTICS
CHAINS
COMPLEXES
HYPOTHESIS
INTERACTIONS
NUCLEOTIDES
PROTEINS
RIBOSOMES
SPECIFICITY
SUPPORTS
SYNTHESIS