布氏锥虫6-磷酸葡萄糖酸脱氢酶的选择性抑制

Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei.

作者信息

Bertelli M, El-Bastawissy E, Knaggs M H, Barrett M P, Hanau S, Gilbert I H

机构信息

Dipartimento di Biochimica e Biologia molecolare, Universita di Ferrara, Italy.

出版信息

J Comput Aided Mol Des. 2001 May;15(5):465-75. doi: 10.1023/a:1011196508214.

DOI:10.1023/a:1011196508214

PMID:11394739

Abstract

A number of triphenylmethane derivatives have been screened against 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Some of these compounds show good inhibition of the enzymes and also selectivity towards the parasite enzyme. Modelling was undertaken to dock the compounds into the active sites of both enzymes. Using a combination of DOCK 3.5 and FLEXIDOCK a correlation was obtained between docking score and both activity for the enzymes and selectivity. Visualisation of the docked structures of the inhibitors in the active sites of the enzymes yielded a possible explanation of the selectivity for the parasite enzyme.

摘要

已针对布氏锥虫和绵羊肝脏中的6-磷酸葡萄糖酸脱氢酶筛选了多种三苯甲烷衍生物。其中一些化合物对这些酶表现出良好的抑制作用，并且对寄生虫酶具有选择性。进行了建模以将这些化合物对接至两种酶的活性位点。使用DOCK 3.5和FLEXIDOCK的组合，获得了对接分数与酶活性和选择性之间的相关性。抑制剂在酶活性位点的对接结构可视化，为寄生虫酶的选择性提供了一种可能的解释。