3QGF

Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase complex with (2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid and (2R)-4-(6-chloropyridazin-3-yl)-N-(4-methoxybenzyl)-1-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazine-2-carboxamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.226 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase.

Gentles, R.G.Sheriff, S.Beno, B.R.Wan, C.Kish, K.Ding, M.Zheng, X.Chupak, L.Poss, M.A.Witmer, M.R.Morin, P.Wang, Y.K.Rigat, K.Lemm, J.Voss, S.Liu, M.Pelosi, L.Roberts, S.B.Gao, M.Kadow, J.F.

(2011) Bioorg Med Chem Lett 21: 2212-2215

  • DOI: https://doi.org/10.1016/j.bmcl.2011.03.011
  • Primary Citation of Related Structures:  
    3QGD, 3QGE, 3QGF, 3QGG, 3QGH, 3QGI

  • PubMed Abstract: 

    Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.


  • Organizational Affiliation

    Bristol Myers Squibb, Chemical and Protein Technologies, Wallingford, CT 06492, United States. robert.gentles@bms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
574Hepatitis C virus subtype 1bMutation(s): 0 
Gene Names: NS5B
EC: 2.7.7.48
UniProt
Find proteins for Q9WMX2 (Hepatitis C virus genotype 1b (isolate Con1))
Explore Q9WMX2 
Go to UniProtKB:  Q9WMX2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9WMX2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
23E
Query on 23E

Download Ideal Coordinates CCD File 
C [auth A],
K [auth B]
(2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid
C38 H38 N4 O5
HDBNVTWMHMMKNY-XMHGGMMESA-N
46F
Query on 46F

Download Ideal Coordinates CCD File 
D [auth A],
L [auth B]
(2R)-4-(6-chloropyridazin-3-yl)-N-(4-methoxybenzyl)-1-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazine-2-carboxamide
C24 H23 Cl F3 N5 O5 S
HCWZBSIWWSGFFI-HXUWFJFHSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
M [auth B],
N [auth B],
O [auth B],
P [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.226 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.9α = 90
b = 90.1β = 90
c = 231.3γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing
BUSTERrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-04-20 
  • Deposition Author(s): Sheriff, S.

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description