Biochemistry (Moscow)

, Volume 71, Issue 9, pp 1021–1026

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
Article

DOI: 10.1134/S0006297906090112

Cite this article as:
Kozlov, M.V., Polyakov, K.M., Ivanov, A.V. et al. Biochemistry (Moscow) (2006) 71: 1021. doi:10.1134/S0006297906090112

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.

Key words

hepatitis C virusRNA-dependent RNA polymerasepyrogallol derivativesinhibition mechanismmolecular modeling

Abbreviations

DKA

2,4-dioxo-4-phenylbutanoic acid

CN-DKA

4-[2-(3-cyanopropoxy)phenyl]-2,4-dioxobutanoic acid

Pyr

pyrogallol

CN-Pyr

cyanoacetylhydrazone 5-formylpyrogallol

DMSO

dimethylsulfoxide

HCV

hepatitis C virus

NTP

nucleoside triphosphate

RdRp

RNA-dependent RNA polymerase

Copyright information

© Pleiades Publishing, Inc. 2006

Authors and Affiliations

  • M. V. Kozlov
    • 1
  • K. M. Polyakov
    • 1
  • A. V. Ivanov
    • 1
  • S. E. Filippova
    • 1
  • A. O. Kuzyakin
    • 1
  • V. L. Tunitskaya
    • 1
  • S. N. Kochetkov
    • 1
  1. 1.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia