KINAETIC ISOTOPE EFFECT STUDIES ON REACTIONS OF CD38

CD38是一种与淋巴细胞相关的重要膜抗原 发展并涉及信号转导。这项建议是 旨在通过测量动力学参数来评估CD38过渡态 环状ADP核糖(CADPR)形成的同位素效应 NAD+，由NAD+形成ADP-核糖(ADPR)，以及从NAD+形成ADPR CADPR。所有这些反应都是由30kdal酶催化的。 对这种酶的过渡部位分析有望导致完整的 了解这种酶并提供更好的机会 从过渡态类似物的设计探讨其生物学功能 抑制剂。将获得一系列NAD+类似物变化组的KIE PK/AS将对可用的最佳算法进行系统测试 确定过渡态结构以确定它们是否预测 根据已建立的化学理论的过渡态。

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.