MECHANISMS OF ACYL, PHOSPHORYL AND SULFURYL TRANSFER

描述：(逐字摘自申请人的摘要)酰基的转移， 磷酰基和硫酰基是所有 生物系统。磷酰化转移反应是必不可少的 细胞内的调节功能。硫酸酯化学在 排毒以及在许多调节途径中。酰基转移化学 构成了建筑中和分解过程中的关键反应 蛋白质。这个项目的目标是深入了解 这些反应发生的化学和酶机制，并进入 酶催化这些反应的方式。我们的一些具体目标 包括： 确定溶剂化/去溶化对动力学的影响和 磷酰基和硫酰基转移反应的热力学。确定…… 何种程度的介质效应模拟了酶促磷酸盐的转移和 从溶液到活性中心的硫酸酯底物，以及这种程度 这些效应有助于酶催化。 确定在酶催化条件下是否发生底物辅助催化 磷酰基或硫酰基转移反应。 研究金属磷酸酶的酶机制，并确定其作用 双核金属中心。我们将确定双核金属中心 改变磷酰化转移的机制，或者如果反应类似于 由其他不利用金属离子进行催化的磷酸酶催化。 研究硫基转移反应的反应机理，特别是硫基转移反应 烷基硫酸酯。我们将确定酶促硫酰的反应机理。 通过芳基硫酸酯酶和雌激素磺基转移酶进行转移。 继续我们对酶促酰基转移反应的研究， 底物。我们将继续研究这些机制和过渡 酶促酰基转移的状态与非催化反应的状态进行比较。

DESCRIPTION: (Verbatim from the Applicant's Abstract)The transfers of acyl, phosphoryl and sulfuryl groups are essential chemical processes in all biological systems. Phosphoryl transfer reactions constitute essential regulatory functions in the cell. Sulfate ester chemistry is critical in detoxification as well as in many regulatory pathways. Acyl transfer chemistry constitutes the key reaction in the building and in the decomposition of proteins. The goals of this project are to gain insight into the fundamental chemical and enzymatic mechanisms by which these reactions occur, and into the means by which enzymes catalyze these reactions. Some of our specific goals are: To determine the effects of solvation/desolvation on the kinetics and thermodynamics of phosphoryl and sulfuryl transfer reactions. To ascertain to what degree medium effects mimic the transfer of enzymatic phosphate and sulfate ester substrates from solution to active site, and to what degree such effects contribute to enzymatic catalysis. To determine whether "substrate-assisted" catalysis occurs in enzyme-catalyzed phosphoryl or sulfuryl transfer reactions. To study the enzymatic mechanism of metallophosphatases, and determine the role of the binuclear metal center. We will determine if the binuclear metal center changes the mechanism of phosphoryl transfer, or if the reaction resembles that catalyzed by other phosphatases that do not utilize metal ions for catalysis. To characterize the mechanisms of sulfuryl transfer reactions, particularly of alkyl sulfate esters. We will determine the mechanism of enzymatic sulfuryl transfer by aryl sulfatase and by estrogen sulfotransferase. Continue our study of enzymatic acyl transfer reactions with more specific substrates. We will continue our study of how the mechanisms and transition states for enzymatic acyl transfer compare with those of uncatalyzed reactions.