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: 8169239
• 负责人: DAVID W CHRISTIANSON
• 金额: $ 1.74万
• 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/8169239
• 关键词: Amidohydrolases; Anabolism; Biology; Chemicals; Commit; Complex; Computer Retrieval of Information on Scientific Projects Database; Cyclization; Deacetylase; Enzymes; Evolution; Funding; Gram-Negative Bacteria; Grant; Histone Deacetylase; Human; Institution; Ions; Lipid A; Manganese; Metals; Organic Chemicals; Reaction; Research; Research Personnel; Resources; Site; Source; Specificity; Synchrotrons; System; Terpenes; United States National Institutes of Health; Work; Yersinia enterocolitica; Zinc; arginase; base; chemical reaction; delta-cadinene synthase; farnesyl pyrophosphate; metalloenzyme; mutant; stoichiometry; 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. 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 the substrate farnesyl diphosphate: delta cadinene synthase and site-specific mutants of epi-isozizaene synthase.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们在NE-CAT的工作主要集中在一些金属酶系统，这些系统的晶体质量和尺寸使他们的研究在其他同步辐射源上变得困难。该实验室的一个关键项目集中在双核锰金属酶脱氢酶，以及共享脱氢酶折叠的酶，如锌酶人类组蛋白脱乙酰基酶-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，其催化革兰氏阴性菌中脂质A生物合成的第一个关键步骤。这些金属酶的比较，最终将揭示的化学和结构的基础上的分歧进化的金属离子的特异性和化学计量的酶折叠。此外，我们在NE-CAT的工作集中在萜类环化酶上。这些酶需要金属，催化生物学中最复杂的有机化学反应。 具体而言，我们的工作集中在倍半萜环化酶，催化环化反应，涉及底物法呢基二磷酸：δ杜松烯合酶和表异齐烯合酶的位点特异性突变体。