Structure of PDB 3d28 Chain A Binding Site BS01

Receptor Information

>3d28 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: B34
• InChI: InChI=1S/C21H20N2O4S/c1-13(2)19-20(24)17(21(25)23(19)12-14-8-4-3-5-9-14)18-15-10-6-7-11-16(15)28(26,27)22-18/h3-11,13,19,24H,12H2,1-2H3/t19-/m0/s1
• InChIKey: XKOAFAIRGVAHRA-IBGZPJMESA-N
• SMILES:
  CACTVS 3.341: CC(C)[C@@H]1N(Cc2ccccc2)C(=O)C(=C1O)C3=N[S](=O)(=O)c4ccccc34
  ACDLabs 10.04: O=C4N(Cc1ccccc1)C(C(O)=C4C3=NS(=O)(=O)c2ccccc23)C(C)C
  OpenEye OEToolkits 1.5.0: CC(C)C1C(=C(C(=O)N1Cc2ccccc2)C3=NS(=O)(=O)c4c3cccc4)O
  OpenEye OEToolkits 1.5.0: CC(C)[C@H]1C(=C(C(=O)N1Cc2ccccc2)C3=NS(=O)(=O)c4c3cccc4)O
  CACTVS 3.341: CC(C)[CH]1N(Cc2ccccc2)C(=O)C(=C1O)C3=N[S](=O)(=O)c4ccccc34
• Formula: C21 H20 N2 O4 S
• Name: (5S)-1-benzyl-3-(1,1-dioxido-1,2-benzisothiazol-3-yl)-4-hydroxy-5-(1-methylethyl)-1,5-dihydro-2H-pyrrol-2-one
• ChEMBL: CHEMBL518647
• DrugBank: DB07414
• ZINC: ZINC000100035503
• PDB chain: 3d28 Chain A Residue 579

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3d28 Structure-based design, synthesis, and biological evaluation of 1,1-dioxoisothiazole and benzo[b]thiophene-1,1-dioxide derivatives as novel inhibitors of hepatitis C virus NS5B polymerase.
• Resolution: 2.3 Å
• Binding residue (original residue number in PDB): F193 N316 C366 M414 Y415 Y448 G449 S556
• Binding residue (residue number reindexed from 1): F188 N311 C361 M409 Y410 Y443 G444 S551
• Annotation score: 1
• Binding affinity: MOAD: ic50=1.4uM
  PDBbind-CN: -logKd/Ki=5.85,IC50=1.4uM

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:3d28, PDBe:3d28, PDBj:3d28
• PDBsum: 3d28
• PubMed: 18554907
• UniProt: P26663|POLG_HCVBK Genome polyprotein