Elucidation on Activation and Binding Mechanism of Alcohol Dehydrogenase by Nevirapine
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(Ka)of NVP to ADH was 1.478 × 104 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.
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