Structure of PDB 4w9c Chain L Binding Site BS01

Receptor Information

>4w9c Chain L (length=143) Species: 9606 (Homo sapiens)

VLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKER
CLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQE

Ligand information

• Ligand ID: 3JG
• InChI: InChI=1S/C21H27N3O4/c1-21(2,3)9-19(26)24-12-16(25)8-17(24)20(27)23-10-14-4-6-15(7-5-14)18-11-22-13-28-18/h4-7,11,13,16-17,25H,8-10,12H2,1-3H3,(H,23,27)/t16-,17+/m1/s1
• InChIKey: AWAYHHGNFTVEIB-SJORKVTESA-N
• SMILES:
  OpenEye OEToolkits 1.9.2: CC(C)(C)CC(=O)N1CC(CC1C(=O)NCc2ccc(cc2)c3cnco3)O
  OpenEye OEToolkits 1.9.2: CC(C)(C)CC(=O)N1C[C@@H](C[C@H]1C(=O)NCc2ccc(cc2)c3cnco3)O
  CACTVS 3.385: CC(C)(C)CC(=O)N1C[CH](O)C[CH]1C(=O)NCc2ccc(cc2)c3ocnc3
  CACTVS 3.385: CC(C)(C)CC(=O)N1C[C@H](O)C[C@H]1C(=O)NCc2ccc(cc2)c3ocnc3
  ACDLabs 12.01: O=C(N1CC(O)CC1C(=O)NCc3ccc(c2ocnc2)cc3)CC(C)(C)C
• Formula: C21 H27 N3 O4
• Name: (4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-[4-(1,3-oxazol-5-yl)benzyl]-L-prolinamide
• ChEMBL: CHEMBL3343404
• ZINC: ZINC000098208448
• PDB chain: 4w9c Chain L Residue 301

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4w9c Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities.
• Resolution: 2.2 Å
• Binding residue (original residue number in PDB): W88 Y98 P99 R107 I109 H110 S111 Y112 H115 W117
• Binding residue (residue number reindexed from 1): W27 Y37 P38 R46 I48 H49 S50 Y51 H54 W56
• Annotation score: 1
• Binding affinity: MOAD: Kd=22.2uM
  BindingDB: Kd=22200nM

External links

• PDB: RCSB:4w9c, PDBe:4w9c, PDBj:4w9c
• PDBsum: 4w9c
• PubMed: 25166285
• UniProt: P40337|VHL_HUMAN von Hippel-Lindau disease tumor suppressor (Gene Name=VHL)