奈韦拉平对乙醇脱氢酶催化活性的影响及机制研究  

Elucidation on Activation and Binding Mechanism of Alcohol Dehydrogenase by Nevirapine

作　　者：代露露 张子航 王潇微 蔡蕊蕊 旷琳 冯宇川[1] 吕小兰[1] 庹浔[1] DAI Lulu;ZHANG Zihang;WANG Xiaowei;CAI Ruirui;KUANG Lin;FENG Yuchuan;L Xiaolan;TUO Xun(School of Chemistry and Chemical Engineering,Nanchang University,Nanchang 330000;School of Pharmacy,Nanchang University,Nanchang 330000)

机构地区：[1]南昌大学化学化工学院,江西南昌330000 [2]南昌大学药学院,江西南昌330000

出　　处：《分析科学学报》2024年第2期147-152,共6页Journal of Analytical Science

基　　金：国家自然科学基金(No.31860153);江西省中医药管理局科技计划课题(2022A371);南昌大学校级大学生创新创业训练计划(2022CX081)。

摘　　要：奈韦拉平(Nevirapine,NVP)是一种在临床上用于治疗和预防艾滋病的药物,但NVP会导致肝脏中一些酶的活力异常。乙醇脱氢酶(ADH)是肝脏中一种重要的代谢酶,目前NVP对ADH催化活性的影响尚不清楚。因此,本研究通过光谱学和分子对接技术探究NVP对ADH催化活性的影响及机制。实验结果表明,NVP通过诱导ADH的二级结构发生改变的模式激活ADH的催化活性,并且呈现剂量依赖性。NVP在范德华力和氢键的驱动下进入ADH的辅酶空腔从而形成稳定的二元复合物。热力学实验结果表明两者之间的结合常数为1.478×10^(4)L·mol^(-1)(298K)。此外,NVP与ADH的Leu326、Ile328、Arg48等氨基酸残基之间的Pi-Cation、Pi-Alkyl以及Alkyl作用力在维持复合物稳定性方面同样发挥重要作用。Nevirapine(NVP)is a drug to treat and prevention of AIDS in clinical practice,but the use of NVP may disturb the activity of enzymes in liver.Alcohol dehydrogenase(ADH)is one of the pivotal enzymes in liver.This research intends to investigate the effect of NVP on the activity of ADH and evaluate their structure-activity relationship by spectroscopy experiments and computer simulation.The results revealed that NVP could alter the secondary structure of ADH,leading to a decline in the activity of ADH.And the activated capacity of NVP on ADH activity was concentration dependent.NVP can insert into the position of coenzyme site on ADH to form a binary complex by H-bonds and van der Waals forces.At 298 K,the binding constant(K a)of NVP to ADH was 1.478×10^(4) L·mol^(-1).Moreover,the Pi-Cation force,Pi-Alkyl,and Alkyl force between NVP and the residues of Leu326、Ile328、Arg48 also had key impact on maintaining the stability of NVP-ADH complex.

关 键 词：奈韦拉平 乙醇脱氢酶 多光谱法 分子对接 

分 类 号：O657.3[理学—分析化学]