Structure of PDB 4twy Chain A Binding Site BS01

Receptor Information

>4twy Chain A (length=306)

SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVICTAEDML
NPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQNCLLRLKVDTSNPKTPK
YKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGF
NIDYDCVSFCYMHHMELPTGVHAGTDLEGKFYGPFVDIQTAQAAGTDTTI
TLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDIL
GPLSAQTGIAVLDMCAALKELLQNGMNGRTILGSTILEDEFTPFDVVRQC
SGVTFQ

Ligand information

• Ligand ID: 3BL
• InChI: InChI=1S/C29H34N4O2/c34-19-27(15-26-16-30-20-32-26)31-17-28-14-24-8-4-5-9-25(24)18-33(28)29(35)23-12-10-22(11-13-23)21-6-2-1-3-7-21/h1-3,6-7,10-13,16,19-20,24-25,27-28,31H,4-5,8-9,14-15,17-18H2,(H,30,32)/t24-,25-,27+,28+/m1/s1
• InChIKey: VZCULZJNALRGNB-CZJMETBBSA-N
• SMILES:
  CACTVS 3.385: O=C[C@H](Cc1[nH]cnc1)NC[C@@H]2C[C@H]3CCCC[C@@H]3CN2C(=O)c4ccc(cc4)c5ccccc5
  ACDLabs 12.01: O=CC(NCC3N(C(=O)c2ccc(c1ccccc1)cc2)CC4CCCCC4C3)Cc5cncn5
  OpenEye OEToolkits 1.9.2: c1ccc(cc1)c2ccc(cc2)C(=O)N3CC4CCCCC4CC3CNC(Cc5cnc[nH]5)C=O
  OpenEye OEToolkits 1.9.2: c1ccc(cc1)c2ccc(cc2)C(=O)N3C[C@H]4CCCC[C@@H]4C[C@H]3CN[C@@H](Cc5cnc[nH]5)C=O
  CACTVS 3.385: O=C[CH](Cc1[nH]cnc1)NC[CH]2C[CH]3CCCC[CH]3CN2C(=O)c4ccc(cc4)c5ccccc5
• Formula: C29 H34 N4 O2
• Name: (2S)-2-({[(3S,4aR,8aS)-2-(biphenyl-4-ylcarbonyl)decahydroisoquinolin-3-yl]methyl}amino)-3-(1H-imidazol-5-yl)propanal
• ChEMBL: CHEMBL3402614
• ZINC: ZINC000263621156
• PDB chain: 4twy Chain A Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4twy Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL protease inhibitors
• Resolution: 1.6 Å
• Binding residue (original residue number in PDB): H41 T45 A46 M49 F140 L141 G143 C145 E166
• Binding residue (residue number reindexed from 1): H41 T45 A46 M49 F140 L141 G143 C145 E166
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=3.97,IC50=108uM
  BindingDB: IC50=108000nM

Enzymatic activity

• Catalytic site (original residue number in PDB): H41 G143 C145
• Catalytic site (residue number reindexed from 1): H41 G143 C145
• Enzyme Commision number: 2.1.1.-
  2.1.1.56: mRNA (guanine-N(7))-methyltransferase.
  2.1.1.57: methyltransferase cap1.
  2.7.7.48: RNA-directed RNA polymerase.
  2.7.7.50: mRNA guanylyltransferase.
  3.1.13.-
  3.4.19.12: ubiquitinyl hydrolase 1.
  3.4.22.-
  3.4.22.69: SARS coronavirus main proteinase.
  3.6.4.12: DNA helicase.
  3.6.4.13: RNA helicase.
  4.6.1.-

Gene Ontology

Molecular Function

• GO:0008233 peptidase activity

Biological Process

• GO:0019082 viral protein processing

External links

• PDB: RCSB:4twy, PDBe:4twy, PDBj:4twy
• PDBsum: 4twy
• PubMed: 25614110
• UniProt: P0C6X7|R1AB_SARS Replicase polyprotein 1ab (Gene Name=rep)