ENZYME CATALYSIS OF ELECTRON AND GROUP TRANSFER

这项拨款资助的研究的长远目标是 确定辅酶形成的化学机制 维生素B6(吡哆醛-5‘-磷酸，PLP)、维生素B12 (腺苷钴胺)S-腺苷蛋氨酸(SAM)和[Fe-S]簇 在常规无法解释的反应中的作用 为他们建立的机制。行动的标准机制 PLP的稳定需要碳离子中间体的稳定。一个主要的焦点 这项拨款支持的研究之一就是阐明 PLP在促进底物自由基异构化中的作用 中间体，一种新发现的维生素B6的机械作用。PLP- 促进的自由基重排似乎发生在氨基变位酶 赖氨酸2，3-氨基变位酶，精氨酸2，3-氨基变位酶， D-赖氨酸5，6-氨基变位酶和鸟氨酸氨基变位酶。在…的反应中 L-赖氨酸2，3-氨基变位酶和D-赖氨酸5，6-氨基变位酶 从底物衍生的中间体将被表征 从光谱上看。自组装膜和[Fe-S]团簇在核反应中的作用 自由基形成的启动将被揭开面纱和表征 化学上，光谱上，和动力学上。5‘-脱氧腺苷 由SAM或腺苷钴胺形成的自由基似乎 在两个氨基突变酶中启动自由基重排，这 过程将被描述为特征。肌动蛋白与肌动蛋白之间的关系 维生素B12依赖的氨基变位酶中的腺苷钴胺 另一方面，SAM/[Fe-S]簇依赖的2，3-氨基变位酶将是 已澄清。这项研究的一个重要方面是阐明 维生素B6和B12、SAM和铁的作用的新化学-- 硫磺中心。 氨基突变酶在抗生素的生物合成中起着重要的作用。 催化氨基酸代谢和生物合成的步骤 抗菌素如链霉素F、霉素、杀菌素S和 紫杉醇。β-氨基酸对肌动蛋白功能的贡献 抗生素还不为人所知。β-氨基酸以O-β氨基酰基形式出现 取代基，因此它们为 抗生素分子。有可能正电荷确保了 溶解和促进将抗生素输送到它们的部位 作用，而O-β-氨基酰基可能是生物稳定的。如果 β-氨基酰取代基以这种方式起作用，它们可能成为 重要的药物传递策略，特别是对候选药物 最低限度可溶的物质。

The long term objectives of the research supported by this grant are to determine the chemical mechanisms by which the co-enzyme forms of vitamin B6 (pyridoxal-5'-phosphate, PLP), vitamin B12 (adenosylcobalamin) S-adenosylmethionine (SAM), and [FE-S] clusters function in reactions that cannot be explained by the convention mechanisms established for them. The standard mechanism for the action of PLP entails stabilization of carbanionic intermediates. A major focus of the research supported by this grant is the elucidation of the role of PLP in facilitating isomerizations of substrate radical intermediates, a newly discovered mechanistic role for vitamin B6. PLP- facilitated radical rearrangements appear to take place in aminomutase reactions catalyzed by lysine 2,3-aminomutase, arginine 2,3-aminomutase, D-lysine 5,6-aminomutase and ornithine aminomutase. In the reactions of L-lysine 2,3-aminomutase and D-lysine 5,6-aminomutase, radical intermediates derived from the substrates will be characterized spectroscopically. The roles of SAM and [Fe-S] clusters in the initiation of radical formation will be unmasked and characterized chemically, spectroscopically, and kinetically. 5'-Deoxyadenosyl radical formation from either SAM or adenosylcobalamin appear to initiate the radical rearrangements in the two aminomutases, and this process will be characterized. The relationship between the actin of adenosylcobalamin in vitamin B12-dependent aminomutases on one hand and SAM/[Fe-S] cluster dependent 2,3-aminomutase on the other hand will be elucidated. An important aspect of this research is the elucidation of novel chemistry in the actions of vitamins B6 and B12, SAM, and iron- sulfur centers. Aminomutases play important roles in the biosynthesis of antibiotics. Catalyze steps in amino acid metabolism and the biosynthesis of antibiotics such as Streptothricin F, Mycomycin, Blasticidin S, and Taxol. The contributions of beta-amino acids to the functions of antibiotics are not known. Beta-amino acids appear as O-beta aminoacyl substituents, and as such they contribute positive charges to antibiotic molecules. It is possible that the positive charges ensure solubility and facilitate the delivery of antibiotic to their sites of action, while the O-beta-aminoacyl groups may be biologically stable. If the beta-aminoacyl substituents function in this way, they could become significant in drug delivery strategies, especially for candidate drugs that are minimally soluble.