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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 这是对催化血蛋白机制以及血蛋白结构和活性之间关系的一般研究。这项研究包括但不限于对细胞色素P450，辣根过氧化物酶，乳糖氧化酶，肌红蛋白，肌红蛋白，骨髓过氧化物酶，DUOX酶和血红素氧酶的研究。这些蛋白质研究的关键要素是分析产品结构，立体化学和同位素取代。蛋白质加合物的研究也很重要。除产品研究外，大量使用还由基于机制的和其他不可逆的抑制剂来表征蛋白质活性位点。这些不可逆的抑制剂烷基化烷基化的血红素基团或蛋白质。质谱对于鉴定血红素加合物的结构至关重要，因此对于将基于机理的抑制剂作为结构探针而言。还将鉴定由与蛋白质骨骼反应的药物修饰的蛋白质残基，也被追求是分析活性位点结构和机制的附加工具。与过去一样，这些研究有望为我们对血蛋白机制的理解做出重大贡献，对潜在有用的血蛋白抑制剂的发展以及我们对蛋白质结构和功能的一般理解。