Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei

被引：14

作者：

Bertelli, M

El-Bastawissy, E

Knaggs, MH

Barrett, MP

Hanau, S

Gilbert, IH

机构：

[1] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3XF, S Glam, Wales

[2] Univ Glasgow, IBLS, Div Infect & Immun, Glasgow G12 8QQ, Lanark, Scotland

[3] Univ Ferrara, Dipartimento Biochim & Biol Mol, I-44100 Ferrara, Italy

来源：

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN | 2001年 / 15卷 / 05期

关键词：

docking; enzyme inhibition; selectivity; structure activity relationships; trypanosomiasis;

D O I：

10.1023/A:1011196508214

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：465 / 475

页数：11

共 24 条

[1] CRYSTALLOGRAPHIC STUDY OF COENZYME, COENZYME ANALOG AND SUBSTRATE-BINDING IN 6-PHOSPHOGLUCONATE DEHYDROGENASE - IMPLICATIONS FOR NADP SPECIFICITY AND THE ENZYME MECHANISM [J].