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.

非血清金属的氧酶已显示与A 哺乳动物和细菌的大量代谢过程系统。我们计划的广泛目标是继续我们的分析非血红素铁参与细菌的催化途径双加氧酶，prodocatechute-3,4-二氧酶（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单一氧酶，肝苯丙氨酸羟化酶（PAH），哺乳动物铜单加氧酶，多巴胺β-羟化酶（DBH）和细菌非血红素单加氧酶，P。olevorans环氧酶/羟化酶（poeh）。这些研究中要使用的主要光谱技术是扩展的X射线吸收精细结构（EXAFS）光谱法。在具体目的是（1）使用EXAF来识别性质，数字和铁和铜结合配体的距离；（2）检查活性位点金属与底物，抑制剂，辅助因子的相互作用，和过渡状态类似物；（3）借鉴我们设计的经验过渡状态类似物通过检查新的化合物类似模仿催化中间体，也可以捕获功能参加催化和/或由于结扎的改变而被释放在催化周期中。我们建议获取类型的信息对于理解非血红素金属的分子基础至关重要氧合酶催化和这些特定效应子的设计重要的酶。