Structure of PDB 5pzl Chain B Binding Site BS01

Receptor Information

>5pzl Chain B (length=545) Species: 333284 (Hepatitis C virus (isolate Con1))

SMSYTWTGALITPCVYATTSRSASLRQKKVTFDRLQVLDDHYRDVLKEMK
AKASTVKAKLLSVEEACKLTPPHSARSKFGYGAKDVRNLSSKAVNHIRSV
WKDLLEDTETPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEK
MALYDVVSTLPQAVMGSSYGFQYSPGQRVEFLVNAWKAKKCPMGFAYDTR
CFDSTVTENDIRVEESIYQCCDLAPEARQAIRSLTERLYIGGPLTNSKGQ
NCGYRRCRASGVLTTSCGNTLTCYLKAAAACRAAKLQDCTMLVCGDDLVV
ICESAGTQEDEASLRAFTEAMTRYSAPPGDPPKPEYDLELITSCSSNVSV
AHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWAR
MILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIQRLHGLSAF
SLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRARLLSQGGRAATCG
KYLFNWAVRTKLKLTPIPAASQLDLSSWFVAGYSGGDIYHSLSRA

Ligand information

• Ligand ID: 23E
• InChI: InChI=1S/C38H38N4O5/c43-32-23-42-31-22-26(15-18-29(31)34(25-8-2-1-3-9-25)35(42)28-10-4-5-11-30(28)40-32)36(46)41-38(20-6-7-21-38)37(47)39-27-16-12-24(13-17-27)14-19-33(44)45/h4-5,10-19,22,25H,1-3,6-9,20-21,23H2,(H,39,47)(H,40,43)(H,41,46)(H,44,45)/b19-14+
• InChIKey: HDBNVTWMHMMKNY-XMHGGMMESA-N
• SMILES:
  OpenEye OEToolkits 1.7.0: c1ccc2c(c1)-c3c(c4ccc(cc4n3CC(=O)N2)C(=O)NC5(CCCC5)C(=O)Nc6ccc(cc6)/C=C/C(=O)O)C7CCCCC7
  CACTVS 3.370: OC(=O)/C=C/c1ccc(NC(=O)C2(CCCC2)NC(=O)c3ccc4c(c3)n5CC(=O)Nc6ccccc6c5c4C7CCCCC7)cc1
  ACDLabs 12.01: O=C(O)\C=C\c1ccc(cc1)NC(=O)C7(NC(=O)c4ccc3c(c2c5c(NC(=O)Cn2c3c4)cccc5)C6CCCCC6)CCCC7
  OpenEye OEToolkits 1.7.0: c1ccc2c(c1)-c3c(c4ccc(cc4n3CC(=O)N2)C(=O)NC5(CCCC5)C(=O)Nc6ccc(cc6)C=CC(=O)O)C7CCCCC7
  CACTVS 3.370: OC(=O)C=Cc1ccc(NC(=O)C2(CCCC2)NC(=O)c3ccc4c(c3)n5CC(=O)Nc6ccccc6c5c4C7CCCCC7)cc1
• Formula: C38 H38 N4 O5
• Name: (2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid
• ChEMBL: CHEMBL1738707
• ZINC: ZINC000059826499
• PDB chain: 5pzl Chain B Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5pzl Discovery of a Hepatitis C Virus NS5B Replicase Palm Site Allosteric Inhibitor (BMS-929075) Advanced to Phase 1 Clinical Studies.
• Resolution: 2.06 Å
• Binding residue (original residue number in PDB): L392 A395 A396 H428 L492 G493 V494 P495 R498 V499 W500 R503
• Binding residue (residue number reindexed from 1): L370 A373 A374 H406 L470 G471 V472 P473 R476 V477 W478 R481
• Annotation score: 1

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:5pzl, PDBe:5pzl, PDBj:5pzl
• PDBsum: 5pzl
• PubMed: 28430437
• UniProt: Q9WMX2|POLG_HCVCO Genome polyprotein