title: Movement of the 3'-end of tRNA through the peptidyl transferase centre and its inhibition by antibiotics.
abstract: Determining how antibiotics inhibit ribosomal activity requires a detailed understanding of the interactions and relative movement of tRNA, mRNA and the ribosome. Recent models for the formation of hybrid tRNA binding sites during the elongation cycle have provided a basis for re-evaluating earlier experimental data and, especially, those relevant to substrate movements through the peptidyl transferase centre. With the exception of deacylated tRNA, which binds at the E-site, ribosomal interactions of the 3'-ends of the tRNA substrates generate only a small part of the total free energy of tRNA-ribosome binding. Nevertheless, these relatively weak interactions determine the unidirectional movement of tRNAs through the ribosome and, moreover, they appear to be particularly susceptible to perturbation by antibiotics. Here we summarise current ideas relating particularly to the movement of the 3'-ends of tRNA through the ribosome and consider possible inhibitory mechanisms of the peptidyl transferase antibiotics.
authors.affiliation: RNA Regulation Centre, Institute of Molecular Biology, Copenhagen University, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Kirillov
authors.forename: B T
authors.initials: BT
authors.lastname: Porse
authors.forename: B
authors.initials: B
authors.lastname: Vester
authors.forename: P
authors.initials: P
authors.lastname: Woolley
authors.forename: R A
authors.initials: RA
authors.lastname: Garrett
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000378:metabolism; D010458:Peptidyl Transferases / Q000378:metabolism*; D012329:RNA, Bacterial / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D012329:RNA, Bacterial; D012346:RNA, Transfer, Amino Acyl; D012343:RNA, Transfer; D010458:Peptidyl Transferases