Structure of PDB 4w9e Chain C Binding Site BS01

Receptor Information

>4w9e Chain C (length=141) Species: 9606 (Homo sapiens)

VLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKER
CLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLT

Ligand information

• Ligand ID: 3JT
• InChI: InChI=1S/C21H27N3O3S/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: ZFCSIIZHOAAIJZ-SJORKVTESA-N
• SMILES:
  CACTVS 3.385: CC(C)(C)CC(=O)N1C[CH](O)C[CH]1C(=O)NCc2ccc(cc2)c3scnc3
  OpenEye OEToolkits 1.9.2: CC(C)(C)CC(=O)N1CC(CC1C(=O)NCc2ccc(cc2)c3cncs3)O
  CACTVS 3.385: CC(C)(C)CC(=O)N1C[C@H](O)C[C@H]1C(=O)NCc2ccc(cc2)c3scnc3
  ACDLabs 12.01: O=C(N1CC(O)CC1C(=O)NCc3ccc(c2scnc2)cc3)CC(C)(C)C
  OpenEye OEToolkits 1.9.2: CC(C)(C)CC(=O)N1C[C@@H](C[C@H]1C(=O)NCc2ccc(cc2)c3cncs3)O
• Formula: C21 H27 N3 O3 S
• Name: (4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-[4-(1,3-thiazol-5-yl)benzyl]-L-prolinamide
• ChEMBL: CHEMBL3344078
• ZINC: ZINC000098208454
• PDB chain: 4w9e Chain C Residue 301

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4w9e 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: 2.6 Å
• Binding residue (original residue number in PDB): W88 Y98 P99 I109 H110 S111 Y112 H115 W117
• Binding residue (residue number reindexed from 1): W27 Y37 P38 I48 H49 S50 Y51 H54 W56
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=5.15,Kd=7.09uM
  BindingDB: Kd=7090nM

External links

• PDB: RCSB:4w9e, PDBe:4w9e, PDBj:4w9e
• PDBsum: 4w9e
• PubMed: 25166285
• UniProt: P40337|VHL_HUMAN von Hippel-Lindau disease tumor suppressor (Gene Name=VHL)