Ribosomal antibiotics: structural basis for resistance, synergism and selectivity.
Various antibiotics bind to ribosomes at functionally relevant locations such as the peptidyl-transferase center (PTC) and the exit tunnel for nascent proteins. High-resolution structures of antibiotics bound to ribosomal particles from a eubacterium that is similar to pathogens and an archaeon that shares properties with eukaryotes are deciphering subtle differences in these highly conserved locations that lead to drug selectivity and thereby facilitate clinical usage. These structures also show that members of antibiotic families with structural differences might bind to specific ribosomal pockets in different modes dominated by their chemical properties. Similarly, the chemical properties of drugs might govern variations in the nature of seemingly identical mechanisms of drug resistance. The observed variability in binding modes justifies expectations for structural design of improved antibiotic properties.
Auerbach
Tamar
T
Department of Structural Biology, The Weizmann Institute, 76100 Rehovot, Israel.
Bashan
Anat
A
Yonath
Ada
A
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D001665:Binding Sites; D016503:Drug Delivery Systems / Q000379:methods; D024881:Drug Resistance, Bacterial / Q000276:immunology; D004357:Drug Synergism; D008956:Models, Chemical; D018448:Models, Immunological; D008958:Models, Molecular; D011485:Protein Binding; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000276:immunology*; D012270:Ribosomes / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D012269:Ribosomal Proteins