CRYSTALLOGRAPHIC STUDIES OF HALOARCULA MARISMORTUI RIBOSOMES

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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. The structures of novel antibiotics bound to the 50S subunit of H. marismortui ribosomes will be studied. These drugs do not interfere with the peptidyl transferase reaction and may have a novel mode of action and binding site. Negamycin and girroline are proposed to be inhibitors of the termination reaction. 13-deoxytedanolide is a recently discovered eukaryotic-specific macrolide. These structures may provide insights into new antibiotic target sites. The structures of antibiotic resistance mutations in the 50S will also be studied. Some resistance mutations occur distant to the binding site of the antibiotic, and a structural change may explain this mechanism of antibiotic resistance. We are currently transforming H. marismortui with plasmids containing the rnn operon with G2482A mutation, which confers resistance to chloramphenicol, anisomycin, and sparsomycin.