HYDROXYPROPYLPHOSPHONIC ACID EPOXIDASE (HPPE) BOUND WITH SUBSTRATE ANALOGS

羟丙基膦酸环氧化酶 (HPPE) 与底物类似物结合

• 批准号: 8169296
• 负责人: CATHERINE L DRENNAN
• 金额: $ 0.41万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169296
• 关键词: Acids; Anabolism; Antibiotics; Apoenzymes; Binding; Biological Factors; Biology; Carbon; Computer Retrieval of Information on Scientific Projects Database; Enzymes; Fosfomycin; Funding; Grant; Institution; Multienzyme Complexes; Pathway interactions; Phosphorus; Reaction; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Source; Streptomyces; Structure; Tromethamine; United States National Institutes of Health; analog; epoxidase

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 biosynthetic pathway of the antibiotic fosfomycin is intriguing in that it creates a natural product with a carbon-phosphorus bond and utilizes enzymes whose reactions have no precedent in biology. To investigate this unusual pathway and to probe the unique epoxidation reaction catalyzed by the final biosynthetic enzyme, HppE from Streptomyces wedmorensis, we previously obtained four X-ray structures: the apoenzyme at 2.0 ¿ resolution; a native Fe(II)-bound form at 2.4 ¿ resolution; a tris-(hydroxymethyl)aminomethane-Co(II)-enzyme complex structure at 1.8 ¿ resolution, and a substrate-Co(II)-enzyme complex structure at 2.5 ¿ resolution (in press). Our current studies aim to further elucidate the regiospecific and stereospecific mechanism of fosfomycin biosynthesis using substrates and substrate analogs bound to HppE.

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。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 抗生素磷霉素的生物合成途径很有趣，因为它产生了具有碳-磷键的天然产物，并利用生物学上没有先例的反应的酶来研究这种不寻常的途径并探索最终生物合成所催化的独特环氧化反应。酶，来自韦德莫伦链霉菌的HppE，我们之前获得了四个X射线结构：apoenzyme在2.0 ¿分辨率；天然 Fe(II) 结合形式，2.4 ¿分辨率；三-(羟甲基)氨基甲烷-Co(II)-酶复合物结构，分辨率为 1.8 ¿分辨率，以及底物-Co(II)-酶复合物结构（2.5 ¿）我们目前的研究旨在进一步阐明使用与 HppE 结合的底物和底物类似物进行磷霉素生物合成的区域特异性和立体特异性机制。