MECHANISMS AND INACTIVATION OF HEMOPROTEINS

血蛋白的机制和失活

• 批准号: 8169716
• 负责人: Paul R Ortiz De Montellano
• 金额: $ 0.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169716
• 关键词: Active Sites; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Development; Enzymes; Funding; Grant; Heme; Heme Group; Hemeproteins; Horseradish Peroxidase; Indium; Institution; Investigation; Mass Spectrum Analysis; Myoglobin; Oxygenases; Peroxidases; Proteins; Research; Research Personnel; Resources; Skeleton; Source; Structure; United States National Institutes of Health; adduct; base; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这是对催化血红素蛋白机制以及血红素蛋白结构与活性之间关系的一般研究。这项研究包括但不限于细胞色素 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。这些蛋白质研究的一个关键要素是产品结构、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。除了产品研究之外，还大量使用基于机制的抑制剂和其他不可逆抑制剂来表征蛋白质活性位点。这些不可逆抑制剂使血红素基团或蛋白质烷基化。质谱对于鉴定血红素加合物的结构至关重要，因此对于使用基于机制的抑制剂作为结构探针至关重要。通过与蛋白质骨架反应的试剂修饰的蛋白质残基的鉴定也被作为分析活性位点结构和机制的附加工具。与过去一样，这些研究预计将为我们对血红素蛋白机制的理解、潜在有用的血红素蛋白抑制剂的开发以及我们对蛋白质结构和功能的一般理解做出重大贡献。