Structure of PDB 3h5u Chain B Binding Site BS01

Receptor Information

>3h5u Chain B (length=559) Species: 11105 (Hepatitis C virus (isolate BK))

HMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAGLRQK
KVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSAKSK
FGYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQGR
KPARLIVFPDLGVRVCEKMALYDVVSTLPQVVMGSSYGFQYSPGQRVEFL
VNTWKSKKNPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIK
SLTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACR
AAKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPP
QPEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTP
VNSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSI
EPLDLPQIIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRVWRHRA
RSVRARLLSQGGRAATCGKYLFNWAVKTKLKLTPIPAASRLDLSGWFVAG
YSGGDIYHS

Ligand information

• Ligand ID: H5U
• InChI: InChI=1S/C24H26FN3O6S2/c1-24(2,3)22-20(29)18(23(30)28(22)13-14-8-10-16(25)11-9-14)19-17-7-5-6-15(12-26-35(4,31)32)21(17)36(33,34)27-19/h5-11,22,26,29H,12-13H2,1-4H3/t22-/m1/s1
• InChIKey: ZMOVBEOGACXUBZ-JOCHJYFZSA-N
• SMILES:
  ACDLabs 10.04: Fc1ccc(cc1)CN4C(=O)C(C3=NS(=O)(=O)c2c(cccc23)CNS(=O)(=O)C)=C(O)C4C(C)(C)C
  OpenEye OEToolkits 1.5.0: CC(C)(C)C1C(=C(C(=O)N1Cc2ccc(cc2)F)C3=NS(=O)(=O)c4c3cccc4CNS(=O)(=O)C)O
  OpenEye OEToolkits 1.5.0: CC(C)(C)[C@H]1C(=C(C(=O)N1Cc2ccc(cc2)F)C3=NS(=O)(=O)c4c3cccc4CNS(=O)(=O)C)O
  CACTVS 3.341: CC(C)(C)[CH]1N(Cc2ccc(F)cc2)C(=O)C(=C1O)C3=N[S](=O)(=O)c4c(CN[S](C)(=O)=O)cccc34
  CACTVS 3.341: CC(C)(C)[C@@H]1N(Cc2ccc(F)cc2)C(=O)C(=C1O)C3=N[S](=O)(=O)c4c(CN[S](C)(=O)=O)cccc34
• Formula: C24 H26 F N3 O6 S2
• Name: N-({3-[(5S)-5-tert-butyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-1,1-dioxido-1,2-benzisothiazol-7-yl}methyl)methanesulfonamide
• ChEMBL: CHEMBL578433
• ZINC: ZINC000101287986
• PDB chain: 3h5u Chain B Residue 571

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3h5u Non-nucleoside inhibitors of HCV polymerase NS5B. Part 4: structure-based design, synthesis, and biological evaluation of benzo[d]isothiazole-1,1-dioxides
• Resolution: 1.95 Å
• Binding residue (original residue number in PDB): F193 P197 S288 N291 N316 G317 C366 M414 Y415 I447 Y448 G449 S556
• Binding residue (residue number reindexed from 1): F189 P193 S284 N287 N312 G313 C362 M410 Y411 I443 Y444 G445 S552
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.003uM

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:3h5u, PDBe:3h5u, PDBj:3h5u
• PDBsum: 3h5u
• PubMed: 19709881
• UniProt: P26663|POLG_HCVBK Genome polyprotein