Hepatitis C virus RNA-dependent RNA polymerase: study on the inhibition mechanism by pyrogallol derivatives.
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.
Kozlov
M V
MV
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. kozlovmv@hotmail.com
Polyakov
K M
KM
Ivanov
A V
AV
Filippova
S E
SE
Kuzyakin
A O
AO
Tunitskaya
V L
VL
Kochetkov
S N
SN
D000613:Aminobutyrates / Q000494:pharmacology; D001665:Binding Sites; D002614:Chelating Agents / Q000494:pharmacology; D016174:Hepacivirus / Q000201:enzymology*; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D010654:Phenylbutyrates; D011748:Pyrogallol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*
C515357:2,4-dioxo-4-phenylbutanoic acid; D000613:Aminobutyrates; D002614:Chelating Agents; D010654:Phenylbutyrates; D011748:Pyrogallol; D012324:RNA-Dependent RNA Polymerase; D008274:Magnesium