Structure of PDB 3co9 Chain B Binding Site BS01

Receptor Information

>3co9 Chain B (length=562) Species: 11105 (Hepatitis C virus (isolate BK))

SMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAGLRQK
KVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSAKSK
FGYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQPE
KGGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQVVMGSSYGFQYSPGQR
VEFLVNTWKSKKNPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEAR
QAIKSLTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKAS
AACRAAKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPP
GDPPQPEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETA
RHTPVNSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGA
CYSIEPLDLPQIIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRVW
RHRARSVRARLLSQGGRAATCGKYLFNWAVKTKLKLTPIPAASQLDLSGW
FVAGYSGGDIYH

Ligand information

• Ligand ID: 3MS
• InChI: InChI=1S/C20H23N5O6S2/c1-12(2)8-10-25-20(27)17(18(26)15-5-4-9-24(15)25)19-21-14-7-6-13(22-32(3,28)29)11-16(14)33(30,31)23-19/h4-7,9,11-12,22,26H,8,10H2,1-3H3,(H,21,23)
• InChIKey: FTVCONULIKITPZ-UHFFFAOYSA-N
• SMILES:
  CACTVS 3.341: CC(C)CCN1n2cccc2C(=C(C1=O)C3=Nc4ccc(N[S](C)(=O)=O)cc4[S](=O)(=O)N3)O
  ACDLabs 10.04: O=S(=O)(Nc1ccc2N=C(NS(=O)(=O)c2c1)C4=C(O)c3cccn3N(C4=O)CCC(C)C)C
  OpenEye OEToolkits 1.5.0: CC(C)CCN1C(=O)C(=C(c2n1ccc2)O)C3=Nc4ccc(cc4S(=O)(=O)N3)NS(=O)(=O)C
• Formula: C20 H23 N5 O6 S2
• Name: N-{3-[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydropyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7 -yl}methanesulfonamide;
  N-{3-[4-Hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,2-dihydro-1lambda6-benzo [1,2,4]thiadiazin-7-yl}-methanesulfonamide
• ChEMBL: CHEMBL401974
• DrugBank: DB07062
• ZINC: ZINC000100035122
• PDB chain: 3co9 Chain B Residue 579

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3co9 Pyrrolo[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase.
• Resolution: 2.1 Å
• Binding residue (original residue number in PDB): F193 N291 D318 C366 S368 L384 M414 Y415 Y448 G449 S556
• Binding residue (residue number reindexed from 1): F193 N291 D318 C366 S368 L384 M414 Y415 Y448 G449 S556
• Annotation score: 1
• Binding affinity: BindingDB: IC50=<10nM,EC50=8.5nM

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:3co9, PDBe:3co9, PDBj:3co9
• PDBsum: 3co9
• PubMed: 18487044
• UniProt: P26663|POLG_HCVBK Genome polyprotein