Structure of PDB 3h2l Chain B Binding Site BS01

Receptor Information

>3h2l 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: YAK
• InChI: InChI=1S/C23H23FN4O6S2/c1-35(31,32)26-15-9-10-17-19(11-15)36(33,34)27-22(25-17)20-21(29)16-3-2-4-18(16)28(23(20)30)12-13-5-7-14(24)8-6-13/h5-11,16,18,26,29H,2-4,12H2,1H3,(H,25,27)/t16-,18+/m1/s1
• InChIKey: PAEBVIJMNXTTAT-AEFFLSMTSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)NC(=N2)C3=C(C4CCCC4N(C3=O)Cc5ccc(cc5)F)O
  CACTVS 3.341: C[S](=O)(=O)Nc1ccc2N=C(N[S](=O)(=O)c2c1)C3=C(O)[C@@H]4CCC[C@@H]4N(Cc5ccc(F)cc5)C3=O
  OpenEye OEToolkits 1.5.0: CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)NC(=N2)C3=C([C@@H]4CCC[C@@H]4N(C3=O)Cc5ccc(cc5)F)O
  ACDLabs 10.04: Fc1ccc(cc1)CN4C(=O)C(C3=Nc2c(cc(cc2)NS(=O)(=O)C)S(=O)(=O)N3)=C(O)C5CCCC45
  CACTVS 3.341: C[S](=O)(=O)Nc1ccc2N=C(N[S](=O)(=O)c2c1)C3=C(O)[CH]4CCC[CH]4N(Cc5ccc(F)cc5)C3=O
• Formula: C23 H23 F N4 O6 S2
• Name: N-{3-[(4aR,7aS)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-cyclopenta[b]pyridin-3-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide
• ChEMBL: CHEMBL477014
• ZINC: ZINC000053685061
• PDB chain: 3h2l Chain B Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3h2l Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.
• Resolution: 1.9 Å
• Binding residue (original residue number in PDB): P197 R200 S288 N291 G317 D318 C366 S368 L384 M414 Y415 Y448 S556
• Binding residue (residue number reindexed from 1): P192 R195 S283 N286 G312 D313 C361 S363 L379 M409 Y410 Y443 S551
• 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:3h2l, PDBe:3h2l, PDBj:3h2l
• PDBsum: 3h2l
• PubMed: 19818610
• UniProt: P26663|POLG_HCVBK Genome polyprotein