ANTIBIOTIC RESISTANCE MUTATIONS IN H MARISMORTUI 50S RIBOSOMAL SUBUNITS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们将研究含有氯霉素和茴香霉素耐药突变的H.marismortui 50S核糖体亚基的结构。RNA点突变不会立即发生在两种药物的已知结合部位，而是发生在远离抗生素结合部位的一个或多个碱基上。因此，这些实验将检验这一假设，即微妙的结构重排可能保持形成多肽键所必需的特征，但改变药物的结合位置。还将研究以前未知结合部位和未知机制抑制蛋白质合成终止的新型抗生素吉罗林、尼卡霉素和13-脱氧降糖内酯。

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.