Lactoperoxidase Active Site Structure and Mechanism of Action

Goff 9304926该项目的重点是详细表征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的抑菌产物。 因此，氧化硫氰酸盐中间体的进一步表征将是重要的过氧化物酶抗菌作用的一般理解。 该项目的具体目标包括：（1）乳过氧化物酶的不寻常血红素结构的明确归属;（2）与硫脲衍生物的过氧化物酶代谢相关的活性位点结构修饰的测定;（3）乳过氧化物酶化合物I（双氧化）电子结构的完整描述;和（4）新发现的乳过氧化物酶介导的SCN-氧化产物的鉴定。 哺乳动物血红素过氧化物酶提供了主要的非免疫保护性反应，以抵御入侵的微生物。 白细胞和外分泌流体过氧化物酶利用过氧化氢和卤化物或拟卤化物离子进行抗细菌、寄生虫和病毒的氧化防御。 所提出的研究将描述这些过氧化物酶产生这种氧化抑菌产物的机制，并在一定程度上描述这种机制。 产品 ***

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. ***