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。 未激活的C-H键的羟基化是对基本和实际利益的转变。能够转化的众所周知的酶是利用四个螺旋束蛋白褶皱（Alpha4）的细菌多组分莫糖化酶（BMMS）家族，可将其和4个他的4个羧酸盐配体提供给其二铁的活性位点[1]。我们目前正在研究两种新型的二铁酶，即脱氧蛋白羟化酶（DOHH）和CMLA，它们影响了这种转化。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]都显着偏离BMM的高度保守的结构基序。此外，与BMM不同，DOHH和CMLA仅与蛋白质结合的底物反应，其羟基化严格是立体特异性的。