Brand  (β version)

PDB ID: 4DRU

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Ligands
Code Name Style Show Link
0LN 13-cyclohexyl-3-methoxy-17,22-dimethyl-7h-10,6-(methanoiminothioiminobutanoiminomethano)indolo[2,1-a][2]benzazepine-14,23-dione 16,16-dioxide PoSSuM
SO4 Sulfate ion PoSSuM
GOL Glycerol PoSSuM
Non-standard Residues
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Structure summary

Code : 4DRU   PDBj   RCSB PDB   PDBe
Header : Transferase/Inhibitor
Title : HCV NS5B in complex with macrocyclic INDOLE INHIBITOR
Release Data : 2012-04-18
Compound :
mol_id molecule chains synonym
1 RNA-directed RNA polymerase A,B NS5B, p68
ec: 2.7.7.48
fragment: UNP residues 2420-2982
Source :
mol_id organism_scientific organism_common expression_system
1 Hepatitis C virus  (taxid:420174) HCV Escherichia coli  (taxid:562)
strain: HC-J4
expression_system_strain: Rosetta 2(DE3)
expression_system_plasmid: pet21b
Authors : Cummings, M.D., Vendeville, S.
Keywords : HCV POLYMERASE, macrocycle inhibitor, thumb domain, Transferase-Inhibitor complex
Exp. method : X-RAY DIFFRACTION ( 2.10 Å )
Citation :

Structure-based macrocyclization yields hepatitis C virus NS5B inhibitors with improved binding affinities and pharmacokinetic properties.

Cummings, M.D.,Lin, T.I.,Hu, L.  et al.
(2012)  Angew.Chem.Int.Ed.Engl.  51 : 4637 - 4640

PubMed: 22473861
DOI: 10.1002/anie.201200110

Reaction

Chain : A, B
UniProt : O92972 (POLG_HCVJ4)
Reaction: EC: Evidence:
Physiological Direction:
[Serine protease/helicase NS3]
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'. 		3.4.21.98 UniProtKB:P27958
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[Serine protease/helicase NS3]
a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- diphosphate + phosphate + H(+) 		3.6.1.15 UniProtKB:P27958
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[Serine protease/helicase NS3]
ATP + H2O = ADP + phosphate + H(+) 		3.6.4.13 UniProtKB:P27958
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[RNA-directed RNA polymerase]
RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate 		2.7.7.48 PROSITE-ProRule:PRU00539
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Cofactor: Evidence: Note:
Zn(2+) ECO:0000269 | PubMed:17239391
Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3).
Mg(2+) ECO:0000269 | PubMed:17239391
ECO:0000250 | UniProtKB:Q9WMX2
Binds 1 zinc ion, which has a structural role (PubMed:17239391). The magnesium ion is essential for the helicase activity (By similarity).
Mg(2+) ECO:0000250 | UniProtKB:P26663
Binds 2 magnesium ion that constitute a dinuclear catalytic metal center.