4DRU

HCV NS5B in complex with macrocyclic INDOLE INHIBITOR

PDB DOI: https://doi.org/10.2210/pdb4DRU/pdb

Classification: Transferase/Inhibitor
Organism(s): Hepatitis C virus isolate HC-J4
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2012-02-17 Released: 2012-04-18
Deposition Author(s): Cummings, M.D., Vendeville, S.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.226
R-Value Work: 0.185
R-Value Observed: 0.185

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

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

Cummings, M.D., Lin, T.I., Hu, L., Tahri, A., McGowan, D., Amssoms, K., Last, S., Devogelaere, B., Rouan, M.C., Vijgen, L., Berke, J.M., Dehertogh, P., Fransen, E., Cleiren, E., van der Helm, L., Fanning, G., Van Emelen, K., Nyanguile, O., Simmen, K., Raboisson, P., Vendeville, S.

(2012) Angew Chem Int Ed Engl 51: 4637-4640

PubMed: 22473861 Search on PubMed
DOI: https://doi.org/10.1002/anie.201200110
Primary Citation of Related Structures:
4DRU

Organizational Affiliation

Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. mcummin1@its.jnj.com

Macromolecule Content

Total Structure Weight: 127.91 kDa
Atom Count: 9,474
Modelled Residue Count: 1,108
Deposited Residue Count: 1,126
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
RNA-directed RNA polymerase	A, B	563	Hepatitis C virus isolate HC-J4	Mutation(s): 0 EC: 2.7.7.48
UniProt
Find proteins for O92972 (Hepatitis C virus genotype 1b (strain HC-J4)) Explore O92972 Go to UniProtKB: O92972
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O92972
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
0LN Query on 0LN Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	13-cyclohexyl-3-methoxy-17,22-dimethyl-7H-10,6-(methanoiminothioiminobutanoiminomethano)indolo[2,1-a][2]benzazepine-14,23-dione 16,16-dioxide C₃₂ H₃₈ N₄ O₅ S LTHKMHZATSPXJT-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain J [auth B] SDF format, chain K [auth B] SDF format, chain L [auth B] SDF format, chain M [auth B] SDF format, chain N [auth B] SDF format, chain O [auth B] SDF format, chain P [auth B] SDF format, chain Q [auth B] SDF format, chain R [auth B] SDF format, chain S [auth B] SDF format, chain T [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B]	D [auth A] E [auth A] F [auth A] G [auth A] J [auth B] D [auth A], E [auth A], F [auth A], G [auth A], J [auth B], K [auth B], L [auth B], M [auth B], N [auth B], O [auth B], P [auth B], Q [auth B], R [auth B], S [auth B], T [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain X [auth B] SDF format, chain Y [auth B] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain X [auth B] MOL2 format, chain Y [auth B]	H [auth A] I [auth A] U [auth B] V [auth B] W [auth B] H [auth A], I [auth A], U [auth B], V [auth B], W [auth B], X [auth B], Y [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain I [auth A] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Y [auth B] Interactions & Density Focus chain H [auth A] Focus chain I [auth A] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Y [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
0LN	BindingDB: 4DRU	Kd: 2.4 (nM) from 1 assay(s)
		IC50: 26 (nM) from 1 assay(s)
		EC50: 79 (nM) from 1 assay(s)
	PDBBind: 4DRU	Kd: 2.4 (nM) from 1 assay(s)
	Binding MOAD: 4DRU	Kd: 2.4 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.226
R-Value Work: 0.185
R-Value Observed: 0.185
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 105.13	α = 90
b = 106.643	β = 90
c = 133.286	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-04-18

Deposition Author(s):

Cummings, M.D.

Vendeville, S.

Revision History (Full details and data files)

Version 1.0: 2012-04-18
Type: Initial release
Version 1.1: 2012-08-15
Changes: Database references
Version 1.2: 2024-02-28
Changes: Data collection, Database references, Derived calculations