, Volume 71, Issue 9, pp 1021-1026

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

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Abstract

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.

Original Russian Text © M. V. Kozlov, K. M. Polyakov, A. V. Ivanov, S. E. Filippova, A. O. Kuzyakin, V. L. Tunitskaya, S. N. Kochetkov, 2006, published in Biokhimiya, 2006, Vol. 71, No. 9, pp. 1253–1259.
Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM06-072, June 11, 2006.