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; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 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环化合酶上，这些曲替烯环酶催化涉及底物farnesyl二磷酸盐的环化反应：三角洲核合酶和epi-Esozizaene合酶的位点特异性突变体。