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

M V Kozlov; K M Polyakov; A V Ivanov; S E Filippova; A O Kuzyakin; V L Tunitskaya; S N Kochetkov

doi:10.1134/s0006297906090112

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

Biochemistry (Mosc). 2006 Sep;71(9):1021-6. doi: 10.1134/s0006297906090112.

Authors

M V Kozlov¹, K M Polyakov, A V Ivanov, S E Filippova, A O Kuzyakin, V L Tunitskaya, S N Kochetkov

Affiliation

¹ Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. [email protected]

PMID: 17009957
DOI: 10.1134/s0006297906090112

Abstract

Pyrogallol reversibly and noncompetitively inhibits the activity of the hepatitis C RNA-dependent RNA polymerase. 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminobutyrates / pharmacology
Binding Sites
Chelating Agents / pharmacology
Hepacivirus / enzymology*
Magnesium / chemistry
Models, Molecular
Phenylbutyrates
Pyrogallol / analogs & derivatives*
Pyrogallol / pharmacology*
RNA-Dependent RNA Polymerase / antagonists & inhibitors*

Substances

2,4-dioxo-4-phenylbutanoic acid
Aminobutyrates
Chelating Agents
Phenylbutyrates
Pyrogallol
RNA-Dependent RNA Polymerase
Magnesium