Structure of PDB 5nvy Chain L Binding Site BS01

Receptor Information

>5nvy Chain L (length=143) Species: 9606 (Homo sapiens)

VLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKER
CLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQE

Ligand information

• Ligand ID: 9B5
• InChI: InChI=1S/C21H26N4O4S/c1-12-19(30-11-23-12)16-6-4-15(5-7-16)9-22-20(28)18-8-17(27)10-25(18)21(29)13(2)24-14(3)26/h4-7,11,13,17-18,27H,8-10H2,1-3H3,(H,22,28)(H,24,26)/t13-,17+,18-/m0/s1
• InChIKey: JKHAXURJIZDRKK-VHSSKADRSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: Cc1c(scn1)c2ccc(cc2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C)NC(=O)C)O
  CACTVS 3.385: C[CH](NC(C)=O)C(=O)N1C[CH](O)C[CH]1C(=O)NCc2ccc(cc2)c3scnc3C
  OpenEye OEToolkits 2.0.6: Cc1c(scn1)c2ccc(cc2)CNC(=O)C3CC(CN3C(=O)C(C)NC(=O)C)O
  CACTVS 3.385: C[C@H](NC(C)=O)C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc2ccc(cc2)c3scnc3C
• Formula: C21 H26 N4 O4 S
• Name: (2~{S},4~{R})-1-[(2~{S})-2-acetamidopropanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide
• ChEMBL: CHEMBL4227864
• PDB chain: 5nvy Chain L Residue 301

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5nvy Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298).
• Resolution: 2.9 Å
• Binding residue (original residue number in PDB): F76 W88 Y98 R107 I109 H110 S111 Y112 H115 W117
• Binding residue (residue number reindexed from 1): F15 W27 Y37 R46 I48 H49 S50 Y51 H54 W56
• Annotation score: 1
• Binding affinity: BindingDB: IC50=21200nM

External links

• PDB: RCSB:5nvy, PDBe:5nvy, PDBj:5nvy
• PDBsum: 5nvy
• PubMed: 28853884
• UniProt: P40337|VHL_HUMAN von Hippel-Lindau disease tumor suppressor (Gene Name=VHL)