title: Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli 23S ribosomal RNA.
abstract: Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli ribosomes has been compared by chemical footprinting. The protection afforded by both drugs is limited to the peptidyl transferase loop of 23S rRNA. Under conditions of stoichiometric binding at 1 mM drug concentration in vitro, both drugs strongly protect 23S rRNA bases A2058 and A2451 from dimethyl sulphate and G2505 from kethoxal modification; G2061 is also weakly protected from kethoxal. The modification patterns differ in that A2059 is additionally protected by clindamycin but not by lincomycin. The affinity of the two drugs for the ribosome, estimated by footprinting, is approximately the same, giving Kdiss values of 5 microM for lincomycin and 8 microM for clindamycin. The results show that in vitro the drugs are equally potent in blocking their ribosomal target site. Their inhibitory effects on peptide bond formation could, however, be subtly different.
authors.affiliation: Department of Molecular Biology, Odense University, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Douthwaite
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002981:Clindamycin / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D008034:Lincomycin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012338:RNA, Ribosomal, 23S / Q000187:drug effects* / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D012338:RNA, Ribosomal, 23S; D002981:Clindamycin; D008034:Lincomycin; D012194:RNA-Directed DNA Polymerase