Hepatitis C virus RNA-dependent RNA polymerase: Study on the inhibition mechanism by pyrogallol derivatives

被引：7
|
作者：
Kozlov, M. V. [1 ]
Polyakov, K. M. [1 ]
Ivanov, A. V. [1 ]
Filippova, S. E. [1 ]
Kuzyakin, A. O. [1 ]
Tunitskaya, V. L. [1 ]
Kochetkov, S. N. [1 ]
机构：
[1] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia
来源：
BIOCHEMISTRY-MOSCOW | 2006年 / 71卷 / 09期
基金：
俄罗斯基础研究基金会;
关键词：
hepatitis C virus; RNA-dependent RNA polymerase; pyrogallol derivatives; inhibition mechanism; molecular modeling;
D O I：
10.1134/S0006297906090112
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：
Pyrogallol reversibly and noncompetitively inhibits the activity of the hepatitis C RNA-dependent RNA polyme rase. Based on molecular modeling of the inhibitor binding in the active site of the enzyme, the inhibition was suggested to be realized via chelation of two magnesium cations involved in the catalysis at the stage of the phosphoryl residue transfer. The proposed model allowed us to purposefully synthesize new derivatives with higher inhibitory capacity.
引用
收藏
页码：1021 / 1026
页数：6
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