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: 8361623
• 负责人: DAVID W CHRISTIANSON
• 金额: $ 1.65万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361623
• 关键词: Amidohydrolases; Anabolism; Biology; Chemicals; Commit; Complex; Cyclization; Deacetylase; Enzymes; Evolution; Funding; Gram-Negative Bacteria; Grant; Histone Deacetylase; Human; Ions; Lipid A; Manganese; Metals; National Center for Research Resources; Organic Chemicals; Principal Investigator; Reaction; Research; Research Infrastructure; Resources; Roentgen Rays; Source; Specificity; Synchrotrons; System; Terpenes; United States National Institutes of Health; Work; Yersinia enterocolitica; Zinc; arginase; base; chemical reaction; cost; ent-kaurene synthetase A; farnesyl pyrophosphate; geranylgeranyl diphosphate; 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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. This work additionally includes the zinc-dependent deacetylase LpxC from Yersinia enterocolitica, which catalyzes the first committed step of lipid A biosynthesis in Gram-negative bacteria. 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 substrates farnesyl diphosphate or geranylgeranyl diphosphate: epi-isozizaene synthase and copalyl diphosphate synthase.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们在 NE-CAT 的工作重点是许多金属酶系统，这些系统的晶体质量和尺寸使得在其他同步加速器源上进行研究变得困难。实验室的一个关键项目侧重于双核锰金属酶精氨酸酶，以及共享精氨酸酶折叠的酶，例如锌酶、人组蛋白脱乙酰酶 8 和细菌乙酰多胺酰胺水解酶。这项工作还包括来自小肠结肠炎耶尔森氏菌的锌依赖性脱乙酰酶 LpxC，它催化革兰氏阴性细菌中脂质 A 生物合成的第一个关键步骤。这些金属酶的比较将最终揭示精氨酸酶折叠中金属离子特异性和化学计量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。这些是需要金属的酶，可催化生物学中最复杂的有机化学反应。 具体来说，我们的工作重点是倍半萜环化酶，其催化涉及底物法尼基二磷酸或香叶基香叶基二磷酸的环化反应：表异齐烯合酶和柯巴基二磷酸合酶。