Structure of PDB 4b74 Chain A Binding Site BS01

Receptor Information

>4b74 Chain A (length=645) Species: 11105 (Hepatitis C virus (isolate BK))

GSVVIVGRIILSGSGSITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQVV
STATQSFLATCVNGVCWTVYHGAGSKTLAGPKGPITQMYTNVDQDLVGWQ
APPGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPVSYLK
GSSGGPLLCPSGHAVGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTD
NSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATL
GFGAYMSKAHGIDPNIRTGVRTITTGAPVTYSTYGKFLADGGCSGGAYDI
IICDECHSTDSTTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNI
EEVALSNTGEIPFYGKAIPIEAIRGGRHLIFCHSKKKCDELAAKLSGLGI
NAVAYYRGLDVSVIPTIGDVVVVATDALMTGYTGDFDSVIDCNTCVTQTV
DFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRRGIYRFVTPGERPSGMF
DSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQDHLEFWESVF
TGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSWDQMWKCLI
RLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSADLEVVT

Ligand information

• Ligand ID: 1LH
• InChI: InChI=1S/C21H27ClFN3O2/c1-3-18(26-14(2)13-19(27)25-12-11-24)16-9-10-17(22)21(20(16)23)28-15-7-5-4-6-8-15/h4-10,14,18,26H,3,11-13,24H2,1-2H3,(H,25,27)/p+2/t14-,18+/m0/s1
• InChIKey: MPOXTYMLTZWDMB-KBXCAEBGSA-P
• SMILES:
  OpenEye OEToolkits 1.7.6: CCC(c1ccc(c(c1F)Oc2ccccc2)Cl)[NH2+]C(C)CC(=O)NCC[NH3+]
  CACTVS 3.370: CC[CH]([NH2+][CH](C)CC(=O)NCC[NH3+])c1ccc(Cl)c(Oc2ccccc2)c1F
  OpenEye OEToolkits 1.7.6: CC[C@H](c1ccc(c(c1F)Oc2ccccc2)Cl)[NH2+][C@@H](C)CC(=O)NCC[NH3+]
  ACDLabs 12.01: Clc2ccc(c(F)c2Oc1ccccc1)C([NH2+]C(C)CC(=O)NCC[NH3+])CC
  CACTVS 3.370: CC[C@@H]([NH2+][C@@H](C)CC(=O)NCC[NH3+])c1ccc(Cl)c(Oc2ccccc2)c1F
• Formula: C21 H29 Cl F N3 O2
• Name: (2S)-4-[(2-ammonioethyl)amino]-N-[(1R)-1-(4-chloro-2-fluoro-3-phenoxyphenyl)propyl]-4-oxobutan-2-aminium
• PDB chain: 4b74 Chain A Residue 1721

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4b74 Discovery of an Allosteric Mechanism for the Regulation of Hcv Ns3 Protein Function
• Resolution: 2.18 Å
• Binding residue (original residue number in PDB): V78 D79 D81 R155 M485 F486 Y516 L517 T519 L522 P523 V524 C525 Q526
• Binding residue (residue number reindexed from 1): V92 D93 D95 R169 M499 F500 Y530 L531 T533 L536 P537 V538 C539 Q540
• Annotation score: 1
• Binding affinity: MOAD: Kd=0.022uM
  PDBbind-CN: -logKd/Ki=7.66,Kd=0.022uM

Enzymatic activity

• Catalytic site (original residue number in PDB): T10 C16 H57 D81 G137 S139
• Catalytic site (residue number reindexed from 1): T24 C30 H71 D95 G151 S153
• 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:0004386 helicase activity
• GO:0005524 ATP binding
• GO:0008236 serine-type peptidase activity

Biological Process

• GO:0006508 proteolysis
• GO:0019087 transformation of host cell by virus

External links

• PDB: RCSB:4b74, PDBe:4b74, PDBj:4b74
• PDBsum: 4b74
• PubMed: 23023261
• UniProt: P26663|POLG_HCVBK Genome polyprotein