Lactoperoxidase Active Site Structure and Mechanism of Action

乳过氧化物酶活性位点结构和作用机制

• 批准号: 9304926
• 负责人: Harold Goff
• 金额: $ 27万
• 依托单位: University of Iowa
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9304926&HistoricalAwards=false
• 关键词: Lactoperoxidase; Active; Site; Structure; Mechanism

Goff 9304926 The focus of this project is the detailed characterization of bovine lactoperoxidase active site structural and reactivity properties. The enzyme utilizes hydrogen peroxide and thiocyanate ion to generate an oxidized bacteriostatic product. Hence, further characterization of oxidized thiocyanate intermediates will be of importance to a general understanding of peroxidase antimicrobial action. Specific objectives of this project include: (1) definitive assignment of the unusual heme structure of lactoperoxidase; (2) determination of active site structural modifications associated with peroxidase metabolism of thiocarbamide derivatives; (3) full description of lactoperoxidase compound I (doubly oxidized) electronic structure; and (4) identification of a newly discovered lactoperoxidase-mediated SCN- oxidation product. %%% Mammalian heme peroxidase enzymes provide the major non- immunologic protective response to invading microbes. Leukocyte and exocrine fluid peroxidases utilize hydrogen peroxide and halide or pseudohalide ions for oxidative defense against bacteria, parasites, and viruses. The studies proposed will characterize the mechanism by which these peroxidases generate this oxidized bacteriostatic product and to some extent characterize this product. ***

GoF 9304926这个项目的重点是详细描述牛乳过氧化物酶活性部位的结构和反应特性。该酶利用过氧化氢和硫氰酸根离子生成氧化型抑菌产物。因此，对氧化硫氰酸酯中间体的进一步表征对于全面了解过氧化物酶的抗菌作用具有重要意义。该项目的具体目标包括：(1)确定乳过氧化物酶的不寻常的血红素结构；(2)确定与硫脲类化合物的过氧化物酶代谢有关的活性部位结构修饰；(3)全面描述乳过氧化物酶化合物I(双氧化)的电子结构；以及(4)鉴定新发现的乳过氧化物酶介导的SCN氧化产物。哺乳动物的血红素过氧化物酶对入侵的微生物提供主要的非免疫性保护反应。白细胞和外分泌液过氧化物酶利用过氧化氢和卤化物或假卤化物离子对细菌、寄生虫和病毒进行氧化防御。建议的研究将表征这些过氧化物酶产生这种氧化抑菌产物的机制，并在一定程度上表征这种产物。***