ANTIBIOTIC RESISTANCE MUTATIONS IN H MARISMORTUI 50S RIBOSOMAL SUBUNITS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Structures of H. marismortui 50S ribosomal subunits containing antibitoic resistance mutations for chloramphenicol and anisomycin will be studied. The RNA point mutations do not occur immediately at the known binding sites for either drug, but occur one or more bases distant to the antibiotic binding site. Thus these experiments will test the hypothesis that subtle structural rearrangements may maintain features necessary for peptide bond formation but change the binding site for the drug. Novel antibiotics girolline, negamycin, and 13-deoxytedanolide, which have previously unidentified binding sites and unknown mechanisms of inhibiting protein synthesis termination will also be studied.