STRUCTURE AND FUNCTION OF MYELOPEROXIDASE

髓过氧化物酶的结构和功能

• 批准号: 3296510
• 负责人: MASAO IKEDA-SAITO
• 金额: $ 12.5万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3296510
• 关键词: Raman spectrometry; active sites; atomic absorption spectrometry; calcium binding protein; chlorine; chromophore; enzyme inhibitors; enzyme mechanism; enzyme structure; enzyme substrate; heme; hemoprotein; human tissue; microorganism immunology; myeloperoxidase; neutrophil; nuclear magnetic resonance spectroscopy; photochemistry; protein structure function; thermodynamics

The objective of this application is to delineate the molecular mechanism of the enzyme action. of myeloperoxidase, which is one of the major components of the antimicrobial system of polymorphonuclear neutrophils. One of the important properties of myeloperoxidase is its ability to catalyze the formation of hypochlorous acid from hydrogen peroxide and chloride ion to kill the ingested organism. The primary goals of this research proposal are: (i) determination of the structure of the myeloperoxidase heme group by use of the heme-peptide prepared by proteolytic digestion of the enzyme protein, (ii) characterization of the effect of the specific modification of the heme group on the structure and function of myeloperoxidase by use of the novel photochemically modified myeloperoxidase preparation, and (iii) detailed elucidation of the active site structure of myeloperoxidase with reference to other mammalian peroxidase enzymes to understand the distinct function of this enzyme. We plan to use optical absorption, resonance Raman, electron paramagnetic resonance, nuclear magnetic resonance, and x-ray spectroscopy. Since myeloperoxidase is an central enzyme of oxygen dependent anti-microbial system of neutrophils, elucidation of the molecular mechanism of the enzyme action of myeloperoxidase is essential for our understanding the bactericidal function of polymorphonuclear leukocyte, which is vital for the survival of mammalian species against bacterial infections.

本申请的目的是描绘分子生物学中的分子结构。 酶的作用机制。髓过氧化物酶是一种 多晶型抗菌系统的主要成分 中性粒细胞 髓过氧化物酶的重要特性之一是其 催化氢形成次氯酸的能力 过氧化物和氯离子来杀死摄入的生物体。 首要目标 （一）确定结构; 通过使用通过以下步骤制备的血红素-肽制备髓过氧化物酶血红素基团： （ii）酶蛋白的蛋白水解消化， 血红素基团的特定修饰对结构和 通过使用新型光化学修饰的 髓过氧化物酶制备，和（iii）活性的详细说明 髓过氧化物酶位点结构与其它哺乳动物 过氧化物酶，以了解这种酶的独特功能。 我们 计划使用光学吸收，共振拉曼，电子顺磁 共振、核磁共振和X射线光谱。 以来 髓过氧化物酶是氧依赖性抗微生物剂的中心酶， 中性粒细胞系统，阐明酶的分子机制 髓过氧化物酶的作用对于我们理解 多形核白细胞的杀菌功能， 哺乳动物物种抵抗细菌感染的生存。