X-RAY CRYSTALLOGRAPHIC STUDIES OF METAL-REQUIRING ENZYMES

需要金属的酶的 X 射线晶体学研究

• 批准号: 7955129
• 负责人: DAVID W CHRISTIANSON
• 金额: $ 1.07万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955129
• 关键词: Amidohydrolases; Biology; Chemicals; Complex; Computer Retrieval of Information on Scientific Projects Database; Cyclization; Enzymes; Evolution; Funding; Grant; Histone Deacetylase; Human; Institution; Ions; Manganese; Metals; Organic Chemicals; Reaction; Research; Research Personnel; Resources; Roentgen Rays; Source; Specificity; Synchrotrons; System; Terpenes; United States National Institutes of Health; Work; Zinc; arginase; base; chemical reaction; delta-cadinene synthase; farnesyl pyrophosphate; metalloenzyme; stoichiometry; structural biology; trichodiene synthase

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. Our work at NE-CAT has focused on a number of metalloenzyme systems for which crystal quality and size make their study difficult at other synchrotron sources. A key project in the lab focuses on the binuclear manganese metalloezyme arginase, as well as enzymes that share the arginase fold such as the zinc enzymes human histone deacetylase-8 and bacterial acetylpolyamine amidohydrolase. Comparisons of these metalloenzymes will ultimately reveal the chemical and structural basis for the divergent evolution of metal ion specificity and stoichiometry in the arginase fold. Additionally, our work at NE-CAT has focused on terpenoid cyclases. These are metal-requiring enzymes that catalyze the most complex organic chemical reactions in biology. Specifically, our work has focused on sesquiterpene cyclases that catalyze cyclization reactions involving the substrate farnesyl diphosphate: germacradienol synthase and delta cadinene synthase.

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。 我们在NE-CAT的工作集中在一些金属酶系统上，对于这些系统，晶体质量和大小使得他们在其他同步加速器源上的研究变得困难。该实验室的一个关键项目专注于双核锰金属酶精氨酸酶，以及共享精氨酸酶折叠的酶，如锌酶人组蛋白脱乙酰基酶-8和细菌乙酰多胺氨基水解酶。对这些金属酶的比较将最终揭示精氨酸酶折叠中金属离子专一性和化学计量比差异进化的化学和结构基础。此外，我们在NE-CAT的工作重点是萜类环化酶。这些都是需要金属的酶，催化生物中最复杂的有机化学反应。具体地说，我们的工作集中在催化涉及底物法尼基二磷酸的环化反应的倍半萜环化酶：GermacRadienol合成酶和Delta Cadinene合成酶。