CRYSTALLOGRAPHIC STUDIES OF HALOARCULA MARISMORTUI RIBOSOMES

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。 我们将研究结合在马来丝虫核糖体50S亚单位上的新型抗生素的结构。这些药物不干扰肽基转移酶反应，可能具有新的作用模式和结合部位。奈加霉素和吉罗林被认为是终止反应的抑制剂。13-脱氧萜内酯是最近发现的一种真核特异性大环内酯类化合物。这些结构可能为新的抗生素靶点提供洞察力。还将研究50年代抗生素耐药性突变的结构。一些耐药性突变发生在远离抗生素结合部位的地方，结构变化可能解释了这种抗生素耐药性的机制。我们目前正在用含有带有G2482A突变的RNN操纵子的质粒转化海参，G2482A突变使其对氯霉素、茴香霉素和司帕霉素产生抗药性。

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.