STRUCTURAL MODELS FOR MOLYBDOENZYMES

钼酶的结构模型

• 批准号: 2178972
• 负责人: JOHN H ENEMARK
• 金额: $ 20.01万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-06-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178972
• 关键词: X ray crystallography; chemical models; chemical synthesis; circular dichroism; electrochemistry; electron spin resonance spectroscopy; electron transport; enzyme structure; heme; metal complex; metalloenzyme; molybdenum; nuclear magnetic resonance spectroscopy; porphyrins; sulfites

Molybdenum is an essential trace element that is found in enzymes involved in purine metabolism, sulfur metabolism, and the assimilation of inorganic nitrogen. Exposure to excess molybdenum has been linked with gout, and molybdenum levels in the soil affect the levels of nitrate and nitrite and also interfere with normal copper metabolism. In humans, fatal simultaneous deficiencies in enzyme activity for xanthine oxidase and sulfite oxidase have been shown to result from an inborn deficiency of the "molybdenum cofactor," an essential constituent of both enzymes. This research is directed toward understanding this common molybdenum cofactor, which is thought to be a monomeric molybdenum center with ligating sulfur atoms. One objective of this research is to synthesize and to structurally, chemically and spectroscopically characterize molybdenum complexes which are models for the molybdenum centers of these enzymes. Special emphasis will be given to complexes containing a monomeric oxo-molybdenum center linked to an iron porphyrin center as a model for sulfite oxidase. The compounds and their reactions with substrates and inhibitors of molybdoenzymes win be studied by electron paramagnetic resonance spectroscopy (EPR), spectroelectrochemistry, electronic spectroscopy and x-ray crystallography. A second objective is to directly investigate the molybdenum center of the enzyme sulfite oxidase by studying electron transfer processes between the molybdenum and iron centers of the enzyme and by continuing to grow crystals of sulfite oxidase with the ultimate goal of determining the three dimensional structure of the enzyme.

钼是一种必需的微量元素，存在于参与酶的酶中 嘌呤代谢、硫代谢和无机物同化 氮。 接触过量的钼与痛风有关，并且 土壤中的钼含量影响硝酸盐和亚硝酸盐的含量， 还会干扰正常的铜代谢。 对人类来说，是致命的 黄嘌呤氧化酶和酶活性同时缺乏 亚硫酸盐氧化酶已被证明是由先天性缺陷引起的 “钼辅因子”，两种酶的重要组成部分。 这 研究旨在了解这种常见的钼辅因子， 它被认为是具有配位硫的单体钼中心 原子。 这项研究的目标之一是综合并 钼的结构、化学和光谱表征 复合物是这些酶的钼中心的模型。 将特别强调含有单体的复合物 氧代钼中心与铁卟啉中心相连作为模型 亚硫酸盐氧化酶。 化合物及其与底物的反应 电子顺磁研究钼酶抑制剂 共振光谱 (EPR)、光谱电化学、电子 光谱学和 X 射线晶体学。 第二个目标是直接 通过研究亚硫酸盐氧化酶的钼中心 钼和铁中心之间的电子转移过程 酶并通过继续生长亚硫酸氧化酶晶体 最终目标是确定酶的三维结构。