MECHANISMS AND INACTIVATION OF HEMOPROTEINS

血蛋白的机制和失活

• 批准号: 8363721
• 负责人: Paul R Ortiz De Montellano
• 金额: $ 0.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363721
• 关键词: Active Sites; Cytochrome P450; Development; Enzymes; Funding; Grant; Heme; Heme Group; Hemeproteins; Horseradish Peroxidase; Indium; Investigation; Mass Spectrum Analysis; Myoglobin; National Center for Research Resources; Oxygenases; Peroxidases; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Skeleton; Source; Structure; United States National Institutes of Health; adduct; base; cost; hemoprotein structure; inhibitor/antagonist; lactoperoxidase; protein structure function; stereochemistry; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This is a general investigation of the mechanisms of catalytic hemoproteins and of the relationships between hemoprotein structure and activity. This investigation includes, but is not limited to, studies of the cytochromes P450, horseradish peroxidase, lactoperoxidase, myoglobin, myeloperoxidase, DUOX enzymes, and heme oxygenases. A key element in the study of these proteins is the analysis of product structure, stereochemistry and isotopic substitution. The investigation of protein adducts is also important. In addition to product studies, heavy use is made of mechanism-based and other irreversible inhibitors to characterize the protein active sites. These irreversible inhibitors alkylate either the heme group or the protein. Mass spectrometry is essential for identification of the structures of the heme adducts, and consequently for the use of mechanism-based inhibitors as structural probes. The identification of protein residues that are modified by agents that react with the protein skeleton is also pursued as an additional tool for analysis of the active site structure and mechanism. These investigations, as in the past, are expected to make substantial contributions to our understanding of hemoprotein mechanisms, to the development of potentially useful hemoprotein inhibitors and to our general understanding of protein structure and function.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这是一个关于催化血红素蛋白的机制以及血红蛋白结构和活性之间的关系的一般性研究。这项研究包括但不限于对细胞色素P450、辣根过氧化物酶、乳过氧化物酶、肌红蛋白、髓过氧化物酶、DUOX酶和血红素加氧酶的研究。研究这些蛋白质的一个关键因素是对产物结构、立体化学和同位素取代的分析。蛋白质加合物的研究也很重要。除了产品研究外，还大量使用基于机理的和其他不可逆的抑制剂来表征蛋白质的活性部位。这些不可逆的抑制物可以使血红素基团或蛋白质烷化。质谱学对于鉴定血红素加合物的结构是必不可少的，因此对于使用基于机理的抑制剂作为结构探针是必不可少的。识别被与蛋白质骨架反应的试剂修饰的蛋白质残基也是分析活性部位结构和机制的另一种工具。与过去一样，这些研究有望为我们理解血红素蛋白的机制，开发潜在有用的血红蛋白抑制剂，以及我们对蛋白质结构和功能的总体理解做出实质性贡献。