EXAFS STUDY OF NOVEL NONHEME DIIRON HYDROXYLASES

新型非血红素二铁羟基酶的 EXAFS 研究

• 批准号: 8362383
• 负责人: LAWRENCE QUE, JR
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362383
• 关键词: Active Sites; Enzymes; Family; Funding; Grant; Hydrogen Bonding; Hydroxylation; Ligands; Mixed Function Oxygenases; National Center for Research Resources; Principal Investigator; Protein Binding; Radiation; Research; Research Infrastructure; Resources; Sequence Analysis; Source; Structure; United States National Institutes of Health; carboxylate; cost; deoxyhypusine monooxygenase; interest; novel; protein folding; structural biology

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. The hydroxylation of unactivated C-H bond is a transformation of great fundamental and practical interest. A well known class of enzymes capable of this transformation is the bacterial multicomponent mooxygenases (BMMs)family utilizing four-helix bundle protein folds (alpha4) to provide 2 His and 4 carboxylate ligands to their diiron active sites [1]. We are currently investigating two novel diiron enzymes, deoxyhypusine hydroxylase (DOHH) and CmlA, that effect this transformation. Although crystal structures of these two enzymes have not been obtained, sequence analysis indicates that both DOHH [2] and CmlA [3] remarkably deviate from the highly conserved structural motif of BMMs. In addition, unlike BMMs, DOHH and CmlA only react with protein-bound substrates and their hydroxylation is strictly stereospecific.

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 并且子项目的首席研究员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。 未活化的C-H键的羟基化是一种具有重大基础和实际意义的转变。能够进行这种转化的一类众所周知的酶是细菌多组分单加氧酶 (BMM) 家族，利用四螺旋束蛋白折叠 (α4) 为其二铁活性位点提供 2 个组氨酸和 4 个羧酸配体 [1]。我们目前正在研究两种新型二铁酶，即脱氧马尿碱羟化酶 (DOHH) 和 CmlA，它们会影响这种转化。尽管尚未获得这两种酶的晶体结构，但序列分析表明DOHH [2] 和CmlA [3] 均显着偏离BMM 高度保守的结构基序。此外，与 BMM 不同，DOHH 和 CmlA 只与蛋白质结合的底物发生反应，并且它们的羟基化是严格立体特异性的。