MECHANISMS AND INACTIVATION OF HEMOPROTEINS

血蛋白的机制和失活

• 批准号: 7724145
• 负责人: Paul R Ortiz De Montellano
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724145
• 关键词: Active Sites; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Development; Funding; Grant; Heme; Heme Group; Hemeproteins; Horseradish Peroxidase; Indium; Institution; Investigation; Mass Spectrum Analysis; Modification; Myoglobin; Oxygen; Oxygenases; Peroxidase; Proteins; Research; Research Personnel; Resources; Skeleton; Source; Structure; United States National Institutes of Health; adduct; base; hemoprotein structure; inhibitor/antagonist; lactoperoxidase; protein structure function; sensor; 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, heme oxygenases, and oxygen sensors. 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. The studies also include analysis of the autocatalytic intramolecular modifications that occur in hemoproteins. These investigations 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 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，血红素氧酶和氧气传感器的研究。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。研究还包括对血蛋白中发生的自催化分子内修饰的分析。预计这些研究将对我们对血蛋白机制的理解，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做出重大贡献。