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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们在NE-CAT的工作集中在许多金属酶系统上，晶体质量和大小使他们的研究难以在其他同步加速器来源。实验室中的一个关键项目侧重于双核锰金属酶精氨酸酶，以及共有精氨酸酶折叠的酶，例如锌酶人组蛋白脱乙酰基酶8和细菌乙酰聚糖胺酰胺氢化酶。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基酶LPXC，它催化了革兰氏阴性细菌中脂质的第一个生物合成的步骤。这些金属酶的比较最终将揭示金属离子特异性和精氨酸酶折叠中金属特异性分歧演化的化学和结构基础。此外，我们在NE-CAT的工作集中在萜类化合酶上。这些是催化生物学中最复杂的有机化学反应的金属征用酶。 具体而言，我们的工作集中在倍半萜烯循环酶上，这些环烯循环酶催化涉及底物的底板二磷酸二磷酸或黄烷基凝酰二磷酸的反应：Epi-Isozizaene合酶和Copalyl二磷酸二磷酸合酶。