KINAETIC ISOTOPE EFFECT STUDIES ON REACTIONS OF CD38

CD38反应的动力学同位素效应研究

• 批准号: 2872636
• 负责人: ANTHONY A. SAUVE
• 金额: $ 2.58万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2872636
• 关键词: CD38 molecule; catalyst; chemical kinetics; chemical transfer reaction; electronic spectra; enzyme mechanism; glycoprotein structure; hydrolysis; nonradiation isotope effect

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.

CD38是与淋巴细胞相关的重要膜抗原 发育并参与信号转导。这个提议是 旨在通过测量动力学来评估 CD38 过渡态 同位素效应 (KIE) 形成环状 ADP 核糖 (cADPR) NAD+，从 NAD+ 形成 ADP-核糖 (ADPR)，以及从 NAD+ 形成 ADPR CADPR。所有这些反应均由 30kdal 酶催化。 这种酶的转换位点分析有望产生完整的 了解这种酶并提供更好的机会 通过过渡态类似物的设计探讨其生物学功能 抑制剂。一系列不同组的 NAD+ 类似物的 KIE pK/as 将为可用的最佳算法提供系统测试 过渡态结构确定以确定它们是否预测 根据已建立的化学理论的过渡态。