Structure of PDB 4tww Chain B Binding Site BS01

Receptor Information

>4tww Chain B (length=306)

SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVICTAEDML
NPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQNCLLRLKVDTSNPKTPK
YKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGF
NIDYDCVSFCYMHHMELPTGVHAGTDLEGKFYGPFVDIQTAQAAGTDTTI
TLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDIL
GPLSAQTGIAVLDMCAALKELLQNGMNGRTILGSTILEDEFTPFDVVRQC
SGVTFQ

Ligand information

• Ligand ID: 3A7
• InChI: InChI=1S/C23H29BrN4O2/c24-19-7-5-16(6-8-19)23(30)28-13-18-4-2-1-3-17(18)9-22(28)12-26-21(14-29)10-20-11-25-15-27-20/h5-8,11,14-15,17-18,21-22,26H,1-4,9-10,12-13H2,(H,25,27)/t17-,18-,21+,22+/m1/s1
• InChIKey: SKLHMRHVVDDIOX-UBBRYJJRSA-N
• SMILES:
  CACTVS 3.385: Brc1ccc(cc1)C(=O)N2C[C@H]3CCCC[C@@H]3C[C@H]2CN[C@@H](Cc4[nH]cnc4)C=O
  ACDLabs 12.01: Brc1ccc(cc1)C(=O)N3C(CC2C(CCCC2)C3)CNC(C=O)Cc4cncn4
  OpenEye OEToolkits 1.9.2: c1cc(ccc1C(=O)N2C[C@H]3CCCC[C@@H]3C[C@H]2CN[C@@H](Cc4cnc[nH]4)C=O)Br
  CACTVS 3.385: Brc1ccc(cc1)C(=O)N2C[CH]3CCCC[CH]3C[CH]2CN[CH](Cc4[nH]cnc4)C=O
  OpenEye OEToolkits 1.9.2: c1cc(ccc1C(=O)N2CC3CCCCC3CC2CNC(Cc4cnc[nH]4)C=O)Br
• Formula: C23 H29 Br N4 O2
• Name: (2S)-2-({[(3S,4aR,8aS)-2-(4-bromobenzoyl)decahydroisoquinolin-3-yl]methyl}amino)-3-(1H-imidazol-5-yl)propanal
• ChEMBL: CHEMBL3402618
• ZINC: ZINC000223775894
• PDB chain: 4tww Chain B Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4tww Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL protease inhibitors
• Resolution: 2.42 Å
• Binding residue (original residue number in PDB): M49 F140 L141 N142 G143 S144 C145 H163 E166
• Binding residue (residue number reindexed from 1): M49 F140 L141 N142 G143 S144 C145 H163 E166
• Annotation score: 1
• Binding affinity: MOAD: ic50=63uM
  PDBbind-CN: -logKd/Ki=4.20,IC50=63uM
  BindingDB: IC50=63000nM

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