MECHANISMS OF ACYL, PHOSPHORYL AND SULFURYL TRANSFER

描述：（逐字引用申请人的摘要）酰基的转移， 磷酰基和硫酰基是所有化学过程中的基本化学过程。 生物系统。磷酰基转移反应构成了 细胞中的调节功能。硫酸酯化学是关键， 解毒以及许多调节途径。酰基转移化学 构成了建筑和分解的关键反应， proteins.这个项目的目标是深入了解基本的 化学和酶的机制，这些反应发生，并进入 酶催化这些反应的方法。我们的一些具体目标 为： 为了确定溶剂化/去溶剂化对动力学的影响， 磷酰基和硫酰基转移反应的热力学。查明 介质效应模拟酶促磷酸盐转移的程度， 硫酸酯底物从溶液到活性位点，以及在何种程度上， 作用有助于酶催化。 为了确定“底物辅助”催化是否发生在酶催化的 磷酰基或硫酰基转移反应。 研究金属磷酸酶的酶学机制，确定其在植物生长中的作用 双核金属中心我们将确定双核金属中心 改变磷酰基转移的机制，或者如果反应类似于 由不利用金属离子进行催化的其它磷酸酶催化。 为了表征硫酰基转移反应的机理，特别是 烷基硫酸酯我们将确定酶促硫酰化的机理 通过芳基硫酸酯酶和雌激素磺基转移酶转移。 继续我们的研究，酶的酰基转移反应，更具体的 印刷受体.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.