Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides.
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.
Kondo
Jiro
J
Institut de Biologie Moléculaire et Cellulaire, UPR9002 CNRS, Université Louis Pasteur, 15 rue René Descartes, 67084 Strasbourg, France.
François
Boris
B
Urzhumtsev
Alexandre
A
Westhof
Eric
E
D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D009328:Nebramycin / Q000031:analogs & derivatives / Q000737:chemistry; D010303:Paromomycin / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal / Q000737:chemistry*; D014031:Tobramycin / Q000737:chemistry
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal; D009328:Nebramycin; C011666:apramycin; D010303:Paromomycin; D012313:RNA; D014031:Tobramycin