CRYSTALLOGRAPHIC STUDIES OF HALOARCULA MARISMORTUI RIBOSOMES

HALOARCULA MARISMORTUI 核糖体的晶体学研究

• 批准号: 7602313
• 负责人: SUSAN J SCHROEDER
• 金额: $ 0.36万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7602313
• 关键词: 13-deoxytedanolide; Anisomycin; Antibiotic Resistance; Antibiotics; Binding; Binding Sites; Chloramphenicol; Computer Retrieval of Information on Scientific Projects Database; Distant; Funding; Grant; Haloarcula marismortui; Institution; Macrolides; Mutation; Operon; Peptidyltransferase; Pharmaceutical Preparations; Plasmids; Reaction; Research; Research Personnel; Resistance; Resources; Ribosomes; Site; Source; Sparsomycin; Structure; United States National Institutes of Health; inhibitor/antagonist; insight; negamycin; novel

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 将研究与 H. marismortui 核糖体 50S 亚基结合的新型抗生素的结构。 这些药物不干扰肽基转移酶反应，并且可能具有新的作用模式和结合位点。 Negamycin 和 girroline 被认为是终止反应的抑制剂。 13-deoxytedanolide 是最近发现的真核生物特异性大环内酯。 这些结构可以为新的抗生素靶位点提供见解。 还将研究 50 年代抗生素耐药性突变的结构。 一些耐药突变发生在远离抗生素结合位点的地方，结构变化可以解释这种抗生素耐药机制。 我们目前正在用含有 G2482A 突变的 rnn 操纵子的质粒转化 H. marismortui，该突变赋予对氯霉素、茴香霉素和稀疏霉素的抗性。