Structure of PDB 5lli Chain I Binding Site BS01

Receptor Information

>5lli Chain I (length=143) Species: 9606 (Homo sapiens)

VLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKER
CLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQE

Ligand information

• Ligand ID: 6Z3
• InChI: InChI=1S/C27H33N5O4S/c1-16-21(37-15-30-16)18-7-5-17(6-8-18)12-29-23(34)20-11-19(33)13-32(20)24(35)22(26(2,3)4)31-25(36)27(14-28)9-10-27/h5-8,15,19-20,22,33H,9-13H2,1-4H3,(H,29,34)(H,31,36)/t19-,20+,22-/m1/s1
• InChIKey: NDVQUNZCNAMROD-RZUBCFFCSA-N
• SMILES:
  CACTVS 3.385: Cc1ncsc1c2ccc(CNC(=O)[C@@H]3C[C@@H](O)CN3C(=O)[C@@H](NC(=O)C4(CC4)C#N)C(C)(C)C)cc2
  OpenEye OEToolkits 2.0.5: Cc1c(scn1)c2ccc(cc2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)C4(CC4)C#N)O
  OpenEye OEToolkits 2.0.5: Cc1c(scn1)c2ccc(cc2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)C4(CC4)C#N)O
  CACTVS 3.385: Cc1ncsc1c2ccc(CNC(=O)[CH]3C[CH](O)CN3C(=O)[CH](NC(=O)C4(CC4)C#N)C(C)(C)C)cc2
• Formula: C27 H33 N5 O4 S
• Name: (2~{S},4~{R})-1-[(2~{S})-2-[(1-cyanocyclopropyl)carbonylamino]-3,3-dimethyl-butanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide
• ChEMBL: CHEMBL4225537
• PDB chain: 5lli Chain I Residue 301

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5lli Potent and selective chemical probe of hypoxic signalling downstream of HIF-alpha hydroxylation via VHL inhibition.
• Resolution: 2.4 Å
• Binding residue (original residue number in PDB): F76 W88 Y98 I109 H110 S111 Y112 H115 W117
• Binding residue (residue number reindexed from 1): F15 W27 Y37 I48 H49 S50 Y51 H54 W56
• Annotation score: 1
• Binding affinity: MOAD: Kd=90nM
  BindingDB: Kd=90nM,IC50=88nM

External links

• PDB: RCSB:5lli, PDBe:5lli, PDBj:5lli
• PDBsum: 5lli
• PubMed: 27811928
• UniProt: P40337|VHL_HUMAN von Hippel-Lindau disease tumor suppressor (Gene Name=VHL)