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NON-HEME METALLO OXYGENASE CATALYSTS

非血红素金属加氧酶催化剂

基本信息

批准号：
3271665
负责人：
SHELDON W MAY
金额：
$ 16.97万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-04-01 至 1989-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3271665
关键词：
Pseudomonas Raman spectrometry X ray crystallography allosteric site conformation copper enzyme structure enzyme substrate complex iron ligands metalloenzyme nuclear magnetic resonance spectroscopy oxygenases

项目摘要

Non-heme-metal-containing oxygenases have been shown to be involved in a large number of metabolic processes in both mammalian and bacterial systems. The broad objective of our program is to continue our analysis of the involvement of non-heme iron in the catalytic pathway of the bacterial dioxygenases, protocatechuate-3,4-dioxygenase (PCD), and catechol dioxygenase (CTD), and to carry out comparative studies with the mammalian non-heme iron monooxygenase, liver phenylalanine hydroxylase (PAH), the mammalian copper monooxygenase, dopamine-Beta-hydroxylase (DBH), and the bacterial non-heme iron monooxygenase, P. olevorans epoxidase/hydroylase (POEH). The major spectroscopic technique to be used in these studies is extended X-ray absorption fine structure (EXAFS) spectroscopy. Among the specific aims are (1) to use EXAFS to identify the nature, number, and distances of iron and copper-binding ligands; (2) to examine the interaction of active site metals with substrates, inhibitors, cofactors, and transition state analogs; (3) to draw on our experience in designing transition state analogs by examining new classes of compounds designed to mimic catalytic intermediates, and also to trap functionalities which participate in catalysis and/or are freed due to ligation alterations during the catalytic cycle. Information of the type we propose to obtain is essential to an understanding of molecular basis of non-heme metallo oxygenase catalysis and the design of specific effectors for these important enzymes.

非血红素金属加氧酶已被证明参与了一种哺乳动物和细菌中的大量代谢过程系统。我们节目的主要目标是继续我们对非血红素铁在细菌催化途径中的作用双加氧酶、原儿茶酸-3，4-双加氧酶(PCD)和儿茶酚双加氧酶(CTD)，并与哺乳动物进行比较研究非血红素铁单加氧酶、肝苯丙氨酸羟基酶哺乳动物铜单加氧酶、多巴胺-β-羟基酶(DBH)和细菌非血红素铁单加氧酶、白僵菌环氧酶/羟基酶 (POEH)。在这些研究中使用的主要光谱技术是扩展X射线吸收精细结构(EXAFS)光谱。在这些人中具体目标是(1)使用EXAFS来识别性质、数量和铁和铜结合配体的距离；(2)检查活性中心金属与底物、缓蚀剂、辅因子、和过渡态类比；(3)借鉴我们的设计经验通过检查新的化合物类来模拟过渡态模拟催化中间体，并捕捉功能参与催化和/或由于连接改变而自由在催化循环中。我们建议获取的类型的信息对于理解非血红素金属的分子基础是必不可少的加氧酶催化及其特异性效应器的设计重要的酵素。