Structure of PDB 3cwj Chain A Binding Site BS01

Receptor Information

>3cwj Chain A (length=557) Species: 11105 (Hepatitis C virus (isolate BK))

SMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAGLRQK
KVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSAKSK
FGYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQRK
PARLIVFPDLGVRVCEKMALYDVVSTLPQVVMGSSYGFQYSPGQRVEFLV
NTWKSKKNPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIKS
LTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRA
AKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPPQ
PEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPV
NSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIE
PLDLPQIIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRVWRHRAR
SVRARLLSQGGRAATCGKYLFNWAVKTKLKLTPIPAASQLDLSGWFVAGY
SGGDIYH

Ligand information

• Ligand ID: 321
• InChI: InChI=1S/C22H24N4O6S3/c1-13(2)8-9-26-22(28)19(21(27)20(24-26)17-5-4-10-33-17)16-12-35(31,32)18-11-14(25-34(3,29)30)6-7-15(18)23-16/h4-7,10-11,13,25,27H,8-9,12H2,1-3H3
• InChIKey: KLPXSYJOJCQFSY-UHFFFAOYSA-N
• SMILES:
  CACTVS 3.341: CC(C)CCN1N=C(C(=C(C2=Nc3ccc(N[S](C)(=O)=O)cc3[S](=O)(=O)C2)C1=O)O)c4sccc4
  ACDLabs 10.04: O=S(=O)(Nc3ccc4N=C(C1=C(O)C(=NN(C1=O)CCC(C)C)c2sccc2)CS(=O)(=O)c4c3)C
  OpenEye OEToolkits 1.5.0: CC(C)CCN1C(=O)C(=C(C(=N1)c2cccs2)O)C3=Nc4ccc(cc4S(=O)(=O)C3)NS(=O)(=O)C
• Formula: C22 H24 N4 O6 S3
• Name: N-{3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazin-4-yl]-1,1-dioxido-2H-1,4-benzothiazin-7-yl}methanesulfonamide
• ZINC: ZINC000043194715
• PDB chain: 3cwj Chain A Residue 1001

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3cwj 4-(1,1-Dioxo-1,4-dihydro-1lambda6-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-ones as potent inhibitors of HCV NS5B polymerase
• Resolution: 2.4 Å
• Binding residue (original residue number in PDB): F193 P197 S288 N291 N316 D318 C366 L384 G410 N411 M414 Y415 Q446 Y448 S556
• Binding residue (residue number reindexed from 1): F188 P192 S283 N286 N311 D313 C361 L379 G405 N406 M409 Y410 Q441 Y443 S551
• Annotation score: 1
• Binding affinity: MOAD: ic50<0.01uM
  PDBbind-CN: -logKd/Ki=8.00,IC50=10nM
  BindingDB: IC50=<10nM,EC50=11nM

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:3cwj, PDBe:3cwj, PDBj:3cwj
• PDBsum: 3cwj
• PubMed: 18662878
• UniProt: P26663|POLG_HCVBK Genome polyprotein