Structure of PDB 4w9f Chain I Binding Site BS01

Receptor Information

>4w9f Chain I (length=144) Species: 9606 (Homo sapiens)

VLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKER
CLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQER

Ligand information

• Ligand ID: 3JU
• InChI: InChI=1S/C22H29N3O3S/c1-14-20(29-13-24-14)16-7-5-15(6-8-16)11-23-21(28)18-9-17(26)12-25(18)19(27)10-22(2,3)4/h5-8,13,17-18,26H,9-12H2,1-4H3,(H,23,28)/t17-,18+/m1/s1
• InChIKey: BULPVMQBJAMSRN-MSOLQXFVSA-N
• SMILES:
  CACTVS 3.385: Cc1ncsc1c2ccc(CNC(=O)[C@@H]3C[C@@H](O)CN3C(=O)CC(C)(C)C)cc2
  OpenEye OEToolkits 1.9.2: Cc1c(scn1)c2ccc(cc2)CNC(=O)C3CC(CN3C(=O)CC(C)(C)C)O
  OpenEye OEToolkits 1.9.2: Cc1c(scn1)c2ccc(cc2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)CC(C)(C)C)O
  CACTVS 3.385: Cc1ncsc1c2ccc(CNC(=O)[CH]3C[CH](O)CN3C(=O)CC(C)(C)C)cc2
  ACDLabs 12.01: O=C(N1CC(O)CC1C(=O)NCc3ccc(c2scnc2C)cc3)CC(C)(C)C
• Formula: C22 H29 N3 O3 S
• Name: (4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide
• ChEMBL: CHEMBL3344079
• ZINC: ZINC000098208455
• PDB chain: 4w9f Chain I Residue 301

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4w9f 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: 2.1 Å
• Binding residue (original residue number in PDB): F76 P86 W88 Y98 R107 I109 H110 S111 Y112 H115 W117
• Binding residue (residue number reindexed from 1): F15 P25 W27 Y37 R46 I48 H49 S50 Y51 H54 W56
• Annotation score: 1
• Binding affinity: MOAD: Kd=3.27uM
  BindingDB: Kd=3270nM

External links

• PDB: RCSB:4w9f, PDBe:4w9f, PDBj:4w9f
• PDBsum: 4w9f
• PubMed: 25166285
• UniProt: P40337|VHL_HUMAN von Hippel-Lindau disease tumor suppressor (Gene Name=VHL)