PEROXIDASES, CATALASES, AND CYTOCHROME P-450

过氧化物酶、过氧化氢酶和细胞色素 P-450

• 批准号: 3300268
• 负责人: ZBIGNIEW R KORSZUN
• 金额: $ 3.45万
• 依托单位: UNIVERSITY OF WISCONSIN PARKSIDE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3300268
• 关键词: X ray crystallography; catalase; catalyst; cytochrome P450; cytochrome oxidase; heme; oncogenes; oxidation; peroxidases; peroxides; stereochemistry; toxicology

Polarized EXAFS and XANES studies on single crystals of several heme enzymes and model compounds will be-performed. The heme en- zymes include resting and camphor-bound cytochrome p-450 from Ps. putida, and the resting form of yeast cytochrome c peroxidase as well as its cyanide adduct and enzyme-substrate complex. These heme enzymes catalyze a diverse series of rections. Cytochrome c peroxidase catalyzes the breakdown of organic peroxides and ex- hibits catalytic intermediates which are similar in structure and function to catalase and horse radish peroxidase. The cytochromes P-450 catalyze a mixed function bond-breaking of hydrocarbons by cleaving molecular oxygen. This class of enzymes is characterized by a diverse selectivity of substrates and cytochromes P-450 are found in regulatory, oncogenic, and toxological systems. Both the peroxidases and cytochrome P-450 share stereochemical aspects of their catalytic mechanisms and they are similar in certain respects to mitochondrial cytochrome oxidase. A polarized EXAFS study of these enzymes will complement x-ray crystalloqrahic and solution EXAFS studies by providing highly accurate heme in-plane and axial geometries of the catalytic intermediates which are stable in the crystal. ln addition, the measurement of polarized XANES spectra on these enzymes and models coupled with X-Alpha Scattered Wave molecular orbital calculations will provide a description of the electronic basis for catalysis by these enzymes. Finally, the polarized EXAFS and XANES experiments on the model compounds and enzymes will provide a detailed stereochemical decription of the heme second and third nearest neiqhbors.

对几种单晶的偏振 EXAFS 和 XANES 研究 将进行血红素酶和模型化合物。 血红素 en- 酶包括来自 Ps 的静息细胞色素 p-450 和樟脑结合细胞色素 p-450。 恶臭，以及酵母细胞色素 C 过氧化物酶的静止形式 及其氰化物加合物和酶-底物复合物。 这些 血红素酶催化一系列不同的反应。 细胞色素c 过氧化物酶催化有机过氧化物的分解并分解 抑制结构相似的催化中间体 对过氧化氢酶和辣根过氧化物酶起作用。 细胞色素 P-450 通过以下方式催化碳氢化合物的混合功能键断裂 裂解分子氧。 此类酶的特点是 通过底物和细胞色素 P-450 的多种选择性 存在于监管、致癌和毒理学系统中。两者都 过氧化物酶和细胞色素 P-450 具有相同的立体化学特征 它们的催化机制在某些方面是相似的 线粒体细胞色素氧化酶。 一项极化的 EXAFS 研究 这些酶将补充 X 射线晶体和溶液 EXAFS 通过提供高精度平面内和轴向血红素进行研究 催化中间体的几何形状在 水晶。 此外，对这些材料进行偏振 XANES 光谱的测量 酶和模型与 X-Alpha 散射波分子相结合 轨道计算将提供电子的描述 这些酶的催化作用的基础。 最后对模型进行偏振 EXAFS 和 XANES 实验 化合物和酶将提供详细的立体化学 血红素第二和第三最近邻居的描述。