Structure of PDB 3u4r Chain A Binding Site BS01

Receptor Information

>3u4r Chain A (length=558) Species: 420174 (Hepatitis C virus isolate HC-J4)

SMSYTWTGALITPCAAEESKLPINPLSNSLLRHHNMVYATTSRSASLRQK
KVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSIEEACKLTPPHSAKSK
FGYGAKDVRNLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKSEVFCVQRK
PARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPKQRVEFLV
NTWKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIRS
LTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAACRA
AKLQDCTMLVNGDDLVVICESAGTQEDAAALRAFTEAMTRYSAPPGDPPQ
PEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPI
NSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLGKALDCQIYGACYSIE
PLDLPQIIERLHGLSAFTLHSYSPGEINRVASCLRKLGVPPLRTWRHRAR
SVRAKLLSQGGRAAICGRYLFNWAVRTKLKLTPIPAASQLDLSGWFVAGY
SGGDIYHS

Ligand information

• Ligand ID: 08F
• InChI: InChI=1S/C27H23ClN6O6S2/c1-41(37,38)32-18-4-2-5-19(14-18)42(39,40)33-27(36)25-24(20-6-3-10-31-26(20)35)21-13-17(28)7-8-22(21)34(25)15-16-9-11-30-23(29)12-16/h2-14,32H,15H2,1H3,(H2,29,30)(H,31,35)(H,33,36)
• InChIKey: CDTLONANIBXQJQ-UHFFFAOYSA-N
• SMILES:
  OpenEye OEToolkits 1.7.2: CS(=O)(=O)Nc1cccc(c1)S(=O)(=O)NC(=O)c2c(c3cc(ccc3n2Cc4ccnc(c4)N)Cl)C5=CC=CNC5=O
  ACDLabs 12.01: O=S(=O)(Nc1cc(ccc1)S(=O)(=O)NC(=O)c3c(c2cc(Cl)ccc2n3Cc4ccnc(N)c4)C5=CC=CNC5=O)C
  CACTVS 3.370: C[S](=O)(=O)Nc1cccc(c1)[S](=O)(=O)NC(=O)c2n(Cc3ccnc(N)c3)c4ccc(Cl)cc4c2C5=CC=CNC5=O
• Formula: C27 H23 Cl N6 O6 S2
• Name: 1-[(2-aminopyridin-4-yl)methyl]-5-chloro-N-({3-[(methylsulfonyl)amino]phenyl}sulfonyl)-3-(2-oxo-1,2-dihydropyridin-3-yl)-1H-indole-2-carboxamide
• ChEMBL: CHEMBL1934923
• ZINC: ZINC000082164935
• PDB chain: 3u4r Chain A Residue 579

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3u4r II. Novel HCV NS5B polymerase inhibitors: Discovery of indole C2 acyl sulfonamides.
• Resolution: 2.0 Å
• Binding residue (original residue number in PDB): F193 S288 N291 N316 D318 D319 C366 L384 G410 M414 Y415 Y448 G449 S556
• Binding residue (residue number reindexed from 1): F188 S283 N286 N311 D313 D314 C361 L379 G405 M409 Y410 Y443 G444 S551
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.039uM
  PDBbind-CN: -logKd/Ki=7.41,IC50=39nM

Enzymatic activity

• Enzyme Commision number: 2.7.7.48: RNA-directed RNA polymerase.
  3.4.21.98: hepacivirin.
  3.4.22.-
  3.6.1.15: nucleoside-triphosphate phosphatase.
  3.6.4.13: RNA helicase.

Gene Ontology

Molecular Function

• GO:0003723 RNA binding
• GO:0003968 RNA-dependent RNA polymerase activity

Biological Process

• GO:0039694 viral RNA genome replication

External links

• PDB: RCSB:3u4r, PDBe:3u4r, PDBj:3u4r
• PDBsum: 3u4r
• PubMed: 22104146
• UniProt: O92972|POLG_HCVJ4 Genome polyprotein