Enzyme Catalysis of Electron and Group Transfer

描述(申请人提供)：这项由该基金资助的研究的长期目标是确定维生素B6(PLP)、维生素B12(腺苷钴胺)、S-腺苷蛋氨酸(SAM)和铁-硫簇在酶反应中发挥作用的新的化学机制。PLP生物学的传统作用是稳定酶反应中的碳离子中间体。这项拨款支持的研究的一个主要焦点是阐明PLP在涉及自由基-顺磁中间体的反应中的催化作用。PLP促进的自由基反应似乎发生在赖氨酸2，3-氨基变位酶和赖氨酸5，6-氨基变位酶的反应中。底物和维生素辅酶的自由基中间体将被光谱表征，催化它们反应的酶的结构将被阐明。SAM和[4Fe-4S]团簇在自由基形成中的作用将被揭示，并从化学、光谱和动力学方面进行表征。我们将探讨腺苷钴胺在维生素B12依赖和SAM/[4Fe-4S]依赖的氨基变位酶中的作用之间的关系。维生素B6和B12、SAM和[4Fe-4S]的作用将会发现新的化学作用。通过改造产生氨基变位酶的基因，将产生新的β-氨基酸。 氨基变位酶在氨基酸代谢和生物合成中起重要作用。 抗生素如链霉素F、霉素、杀菌素S和紫杉醇。Beta版的贡献- 赖氨酸2，3-氨基变位酶和精氨酸2，3-氨基变位酶产生的氨基酸对功能的影响 抗生素的种类尚不清楚。β-氨基酸可能会在药物开发中发挥重要作用。

DESCRIPTION (provided by applicant): The long term objectives of the research supported by this grant are to determine the novel chemical mechanisms by which vitamin B6 (PLP), Vitamin B12 (adenosylcobalamin), S-adenosylmethionine (SAM), and iron-sulfur clusters function in enzymatic reaction. The conventional role of PLP biology is to stabilize carbanionic intermediates in enzymatic reactions. A major focus of the research supported by this grant is the elucidation of the role of PLP in catalyzing reactions that involve free radical-paramagnetic intermediates. PLP-facilitated radical reactions appear to take place in reactions of aminomutases such as lysine 2,3-aminomutase and lysine 5,6-aminomutase. Radical intermediates of substrates and vitamin coenzymes will be characterized spectroscopically, and the structures of the enzymes that catalyze their reactions will be elucidated. The roles of SAM and [4Fe-4S] clusters in the initiation of radical formation will be unmasked and characterized chemically, spectroscopically, and kinetically. The relationship between the actions of adenosylcobalamin in Vitamin B 12-dependent and SAM/[4Fe-4S]-dependent aminomutases will be explored. Novel chemistry in the actions of vitamins B6 and B12, SAM, and [4Fe-4S] will be discovered. New beta-aminoacids will be produced by engineering of the genes producing aminomutases. Aminomutases are important in amino acid metabolism and the biosynthesis of antibiotics such as Streptothricin F, Myomycin, Blasticidin S, and Taxol. The contributions of beta- amino acids produced by lysine 2,3-aminomutase and arginine 2,3-aminomutase to the functions of antibiotics are not known. The beta-aminoacids may become significant in drug development.