Structure of PDB 3bsc Chain B Binding Site BS01

Receptor Information

>3bsc Chain B (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: 2PD
• InChI: InChI=1S/C23H24N4O5S/c1-14(2)11-12-27-23(29)19(21(28)20(25-27)15-7-5-4-6-8-15)22-24-17-10-9-16(32-3)13-18(17)33(30,31)26-22/h4-10,13-14,28H,11-12H2,1-3H3,(H,24,26)
• InChIKey: HTTWNUWLEOXVKB-UHFFFAOYSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: CC(C)CCN1C(=O)C(=C(C(=N1)c2ccccc2)O)C3=Nc4ccc(cc4S(=O)(=O)N3)OC
  ACDLabs 10.04: O=C4N(N=C(c1ccccc1)C(O)=C4C3=Nc2c(cc(OC)cc2)S(=O)(=O)N3)CCC(C)C
  CACTVS 3.341: COc1ccc2N=C(N[S](=O)(=O)c2c1)C3=C(O)C(=NN(CCC(C)C)C3=O)c4ccccc4
• Formula: C23 H24 N4 O5 S
• Name: 5-hydroxy-4-(7-methoxy-1,1-dioxido-2H-1,2,4-benzothiadiazin-3-yl)-2-(3-methylbutyl)-6-phenylpyridazin-3(2H)-one;
  5-hydroxy-4-(7-methoxy-1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-2-(3-methylbutyl)-6-phenylpyridazin-3(2H)-one
• ChEMBL: CHEMBL255134
• DrugBank: DB06974
• ZINC: ZINC000029128056
• PDB chain: 3bsc Chain B Residue 579

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3bsc Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda6-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 1: exploration of 7'-substitution of benzothiadiazine.
• Resolution: 2.65 Å
• Binding residue (original residue number in PDB): F193 P197 N316 D318 C366 L384 G410 M414 Q446 Y448 S556
• Binding residue (residue number reindexed from 1): F188 P192 N311 D313 C361 L379 G405 M409 Q441 Y443 S551
• Annotation score: 1
• Binding affinity: BindingDB: IC50=33000nM

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:3bsc, PDBe:3bsc, PDBj:3bsc
• PDBsum: 3bsc
• PubMed: 18242088
• UniProt: P26663|POLG_HCVBK Genome polyprotein