KINAETIC ISOTOPE EFFECT STUDIES ON REACTIONS OF CD38

CD 38是与淋巴细胞相关的重要膜抗原 发育和参与信号转导。这项建议是 设计用于通过测量动力学来评估CD 38过渡态 同位素效应（KIE）形成环ADP核糖（cADPR） NAD+、从NAD+形成ADP-核糖（ADPR）和从NAD+形成ADPR CADPR。所有这些反应都由30 kdal酶催化。 这种酶的转换位点分析有望导致一个完整的 了解这种酶，并提供机会， 通过过渡态类似物的设计探讨其生物学功能 抑制剂的一系列NAD+类似物的KIE， pK/as将提供一个系统的测试，最好的算法可用于 过渡态结构测定，以确定它们是否预测 根据已建立的化学理论。

CD38 is an important membrane antigen associated with lymphocyte development and implicated in signal transduction. This proposal is designed to evaluate CD38 transition states by measurement of kinetic isotope effects (KIEs) for formation of cyclic ADP ribose (cADPR) from NAD+, formation of ADP-ribose (ADPR) from NAD+, and formation of ADPR from CADPR. All of these reactions are catalyzed by the 30kdal enzyme. Transition site analysis of this enzyme promises to lead to a complete understanding of this enzyme and to provide the opportunity to better probe its biological function by design of transition state analog inhibitors. KIEs to be obtained for a series of NAD+ analogs varying group pK/as will provide a systematic test for the best algorithms available for transition state structure determination to determine if they predict transition states according to established chemical theory.