Structure of PDB 8e64 Chain A Binding Site BS01

Receptor Information

>8e64 Chain A (length=298) Species: 2697049 (Severe acute respiratory syndrome coronavirus 2)

RKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPN
YEDLLIRKSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKF
VRIQPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNID
YDCVSFCYMHHMELPTGVHAGTDLEGNFYGPFVDRQTAQAAGTDTTITVN
VLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDILGPL
SAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQCS

Ligand information

• Ligand ID: WEL
• InChI: InChI=1S/C25H37N5O8S2/c1-14(2)11-18(21(32)27-19(22(33)40(35,36)37)12-15-9-10-26-20(15)31)30-24(34)38-13-25(3,4)39-23-28-16-7-5-6-8-17(16)29-23/h5-8,14-15,18-19,22,33H,9-13H2,1-4H3,(H,26,31)(H,27,32)(H,28,29)(H,30,34)(H,35,36,37)/t15-,18-,19-,22-/m0/s1
• InChIKey: NRGPZDKZNYWRRP-BCSOYYNPSA-N
• SMILES:
  CACTVS 3.385: CC(C)C[C@H](NC(=O)OCC(C)(C)Sc1[nH]c2ccccc2n1)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@@H](O)[S](O)(=O)=O
  ACDLabs 12.01: CC(C)CC(NC(=O)OCC(C)(C)Sc1nc2ccccc2[NH]1)C(=O)NC(CC1CCNC1=O)C(O)S(=O)(=O)O
  OpenEye OEToolkits 2.0.7: CC(C)CC(C(=O)NC(CC1CCNC1=O)C(O)S(=O)(=O)O)NC(=O)OCC(C)(C)Sc2[nH]c3ccccc3n2
  OpenEye OEToolkits 2.0.7: CC(C)C[C@@H](C(=O)N[C@@H](C[C@@H]1CCNC1=O)[C@@H](O)S(=O)(=O)O)NC(=O)OCC(C)(C)Sc2[nH]c3ccccc3n2
  CACTVS 3.385: CC(C)C[CH](NC(=O)OCC(C)(C)Sc1[nH]c2ccccc2n1)C(=O)N[CH](C[CH]3CCNC3=O)[CH](O)[S](O)(=O)=O
• Formula: C25 H37 N5 O8 S2
• Name: (1S,2S)-2-{[N-({2-[(1H-benzimidazol-2-yl)sulfanyl]-2-methylpropoxy}carbonyl)-L-leucyl]amino}-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid
• PDB chain: 8e64 Chain A Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8e64 Structure-guided design of direct-acting antivirals that exploit the gem-dimethyl effect and potently inhibit 3CL proteases of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and middle east respiratory syndrome coronavirus (MERS-CoV)
• Resolution: 1.75 Å
• Binding residue (original residue number in PDB): F140 G143 C145 H163 H164 M165 E166 Q189 T190
• Binding residue (residue number reindexed from 1): F137 G140 C142 H160 H161 M162 E163 Q186 T187
• Annotation score: 1

Enzymatic activity

• Enzyme Commision number: 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:8e64, PDBe:8e64, PDBj:8e64
• PDBsum: 8e64
• PubMed: 37080108
• UniProt: P0DTD1|R1AB_SARS2 Replicase polyprotein 1ab (Gene Name=rep)