Enzyme Catalysis of Electron and Group Transfer

描述（由申请人提供）：该资助支持的研究的长期目标是确定维生素B6（PLP），维生素B12（腺苷钴胺素），S-腺苷甲硫氨酸（SAM）和铁硫簇在酶促反应中发挥作用的新化学机制。PLP生物学的传统作用是稳定酶促反应中的碳负离子中间体。 这项资助支持的研究的一个主要重点是阐明PLP在催化涉及自由基顺磁性中间体的反应中的作用。 PLP促进的自由基反应似乎发生在氨基变位酶如赖氨酸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]簇在引发自由基形成中的作用将被揭露和表征化学，光谱和动力学。将探讨腺苷钴胺素在维生素B 12依赖性和SAM/[4 Fe-4 S]依赖性氨基变位酶中作用之间的关系。将发现维生素B6和B12、SAM和[4Fe-4S]作用的新化学。新的β-氨基酸将通过改造产生氨基变位酶的基因而产生。 氨基变位酶在氨基酸代谢和生物合成中是重要的。 抗生素如链丝菌素F、肌霉素、杀稻瘟菌素S和紫杉醇。beta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的功能 抗生素是未知的。β-氨基酸可能在药物开发中变得重要。

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.