Structure of PDB 4mkb Chain A Binding Site BS01

Receptor Information

>4mkb Chain A (length=557) Species: 11105 (Hepatitis C virus (isolate BK))

HMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAGLRQK
KVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSAKSK
FGYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQRK
PARLIVFPDLGVRVCEKMALYDVVSTLPQVVMGSSYGFQYSPGQRVEFLV
NTWKSKKNPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIKS
LTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRA
AKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPPQ
PEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPV
NSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIE
PLDLPQIIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRVWRHRAR
SVRARLLSQGGRAATCGKYLFNWAVKTKLKLTPIPAASRLDLSGWFVAGY
SGGDIYH

Ligand information

• Ligand ID: 28V
• InChI: InChI=1S/C24H27N3O4S/c1-24(2,3)21-15-18(20-12-13-25-26-23(20)28)14-17(22(21)31-4)9-6-16-7-10-19(11-8-16)27-32(5,29)30/h6-15,27H,1-5H3,(H,26,28)/b9-6+
• InChIKey: UDTIOWUJACSSAD-RMKNXTFCSA-N
• SMILES:
  ACDLabs 12.01: O=S(=O)(Nc1ccc(cc1)\C=C\c2cc(cc(c2OC)C(C)(C)C)C=3C(=O)NN=CC=3)C
  CACTVS 3.385: COc1c(C=Cc2ccc(N[S](C)(=O)=O)cc2)cc(cc1C(C)(C)C)C3=CC=NNC3=O
  OpenEye OEToolkits 1.7.6: CC(C)(C)c1cc(cc(c1OC)/C=C/c2ccc(cc2)NS(=O)(=O)C)C3=CC=NNC3=O
  OpenEye OEToolkits 1.7.6: CC(C)(C)c1cc(cc(c1OC)C=Cc2ccc(cc2)NS(=O)(=O)C)C3=CC=NNC3=O
  CACTVS 3.385: COc1c(/C=C/c2ccc(N[S](C)(=O)=O)cc2)cc(cc1C(C)(C)C)C3=CC=NNC3=O
• Formula: C24 H27 N3 O4 S
• Name: N-(4-{(E)-2-[3-tert-butyl-2-methoxy-5-(3-oxo-2,3-dihydropyridazin-4-yl)phenyl]ethenyl}phenyl)methanesulfonamide
• ChEMBL: CHEMBL2431466
• ZINC: ZINC000095920965
• PDB chain: 4mkb Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4mkb Discovery of a Novel Series of Potent Non-Nucleoside Inhibitors of Hepatitis C Virus NS5B.
• Resolution: 1.9 Å
• Binding residue (original residue number in PDB): F193 R200 N291 N316 G317 D318 C366 S368 G410 M414 Y415 Q446 I447 Y448 S556
• Binding residue (residue number reindexed from 1): F188 R195 N286 N311 G312 D313 C361 S363 G405 M409 Y410 Q441 I442 Y443 S551
• Annotation score: 1
• Binding affinity: MOAD: ic50=3nM

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:4mkb, PDBe:4mkb, PDBj:4mkb
• PDBsum: 4mkb
• PubMed: 24069953
• UniProt: P26663|POLG_HCVBK Genome polyprotein