Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides.

Jiro Kondo, Boris François, Alexandre Urzhumtsev, Eric Westhof

Institut de Biologie Moléculaire et Cellulaire, UPR9002 CNRS, Université Louis Pasteur, 15 rue René Descartes, 67084 Strasbourg, France.

Nucleic acids symposium series (2004) 2005

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Aminoglycosides are highly effective antibacterial drugs that decrease translation accuracy by binding to the aminoacyl-tRNA decoding site (A site) of 16S ribosomal RNA. On the other hand, they are highly toxic to mammals through kidney and ear-associated illnesses by binding to ribosomal A sites. To understand the mechanism of toxicity of aminoglycosides to mammals at atomic level, crystallographic studies have been carried out with a number of Homo sapiens mitochondrial and cytoplasmic A sites complexed with aminoglycosides. Several X-ray diffraction data sets were successfully collected. Initial phases of mitochondrial A site with tobramycin and cytoplasmic A site with paromomycin were derived by the molecular replacement method. Refinements of atomic parameters are now under progress.

Citation

Jiro Kondo, Boris François, Alexandre Urzhumtsev, Eric Westhof. Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides. Nucleic acids symposium series (2004). 2005(49):253-4