title: Diverse effects of residues 74-78 in ribosomal protein S12 on decoding and antibiotic sensitivity.
abstract: Ribosomal protein S12 plays key roles in the ribosome's response to the error-promoting antibiotic streptomycin and in modulating the accuracy of translation. The discovery that substitutions at His76 in S12, distant from the streptomycin binding site, conferred streptomycin resistance in the thermophilic bacterium Thermus thermophilus prompted us to make similar alterations in the S12 protein of Escherichia coli. While, none of the E. coli S12 mutations confers streptomycin resistance, they all have distinct effects on the accuracy of translation. In addition, a subset of the S12 alterations renders the cells hypersensitive to fusidic acid, an inhibitor of the translocation step of translation. These results indicate that the His 76 region of ribosomal protein S12 plays key roles in tRNA selection and translocation steps of protein synthesis, consistent with its interaction with elongation factors EF-Tu and EF-G, as deduced from structural studies of ribosomal complexes.
authors: School of Biological Sciences, University of Missouri-Kansas City, 5007 Rockhill Rd., Kansas City, MO 64110, United States.
authors: Deepali
authors: D
authors: Agarwal
authors: School of Biological Sciences, University of Missouri-Kansas City, 5007 Rockhill Rd., Kansas City, MO 64110, United States. Electronic address: oconnormi@umkc.edu.
authors: Michael
authors: M
authors: O'Connor
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D014176:Protein Biosynthesis / Q000187:drug effects; D012343:RNA, Transfer / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013307:Streptomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D012269:Ribosomal Proteins; C034212:ribosomal protein S12; D012343:RNA, Transfer; D013307:Streptomycin
keywords: Fusidic acid; Ribosomal protein S12; Streptomycin; Translation fidelity; Translocation