Crystal structure of a complex between the aminoglycoside tobramycin and an oligonucleotide containing the ribosomal decoding a site.
Aminoglycoside antibiotics target the decoding aminoacyl site (A site) on the 16S ribosomal RNA and induce miscoding during translation. Here, we present the crystal structure, at 2.54 A resolution, of an RNA oligonucleotide containing the A site sequence complexed to the 4,6-disubstituted 2-deoxystreptamine aminoglycoside tobramycin. The three aminosugar rings making up tobramycin interact with the deep-groove atoms directly or via water molecules and stabilize a fully bulged-out conformation of adenines A(1492) and A(1493). The comparison between this structure and the one previously solved in the presence of paromomycin confirms the importance of the functional groups on the common neamine part of these two antibiotics for binding to RNA. Furthermore, the analysis of the present structure provides a molecular explanation to some of the resistance mechanisms that have spread among bacteria and rendered aminoglycoside antibiotics inefficient.
Vicens
Quentin
Q
Institut de Biologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique, Modélisation et Simulations des Acides Nucléiques, UPR 9002, Université Louis Pasteur, 15 Rue René Descartes, 67084 Strasbourg Cedex, France.
Westhof
Eric
E
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001665:Binding Sites; D003461:Crystallography; D004926:Escherichia coli / Q000378:metabolism; D008958:Models, Molecular; D009841:Oligonucleotides / Q000737:chemistry*; D010303:Paromomycin / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012336:RNA, Ribosomal, 16S / Q000737:chemistry*; D014031:Tobramycin / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D009841:Oligonucleotides; D012336:RNA, Ribosomal, 16S; D010303:Paromomycin; D014031:Tobramycin