Structure of PDB 6typ Chain A Binding Site BS01

Receptor Information

>6typ Chain A (length=284) Species: 9606 (Homo sapiens)

RLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQVPRSGLAGCVVGGLLY
AVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGVIDGHI
YAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAV
GGFDGTNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGY
DGQDQLNSVERYDVETETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGH
TFLDSVECYDPDTDTWSEVTRMTSGRSGVGVAVT

Ligand information

• Ligand ID: PKG
• InChI: InChI=1S/C28H28N4O3/c1-3-32-25-12-11-23(18(2)27(25)29-30-32)24(16-26(33)34)21-10-9-19-13-14-31(17-22(19)15-21)28(35)20-7-5-4-6-8-20/h4-12,15,24H,3,13-14,16-17H2,1-2H3,(H,33,34)/t24-/m0/s1
• InChIKey: AUCYBCJRRYAJGN-DEOSSOPVSA-N
• SMILES:
  ACDLabs 12.01: c12CCN(Cc1cc(cc2)C(c4c(C)c3nnn(c3cc4)CC)CC(O)=O)C(=O)c5ccccc5
  OpenEye OEToolkits 2.0.7: CCn1c2ccc(c(c2nn1)C)[C@@H](CC(=O)O)c3ccc4c(c3)CN(CC4)C(=O)c5ccccc5
  OpenEye OEToolkits 2.0.7: CCn1c2ccc(c(c2nn1)C)C(CC(=O)O)c3ccc4c(c3)CN(CC4)C(=O)c5ccccc5
  CACTVS 3.385: CCn1nnc2c(C)c(ccc12)[CH](CC(O)=O)c3ccc4CCN(Cc4c3)C(=O)c5ccccc5
  CACTVS 3.385: CCn1nnc2c(C)c(ccc12)[C@@H](CC(O)=O)c3ccc4CCN(Cc4c3)C(=O)c5ccccc5
• Formula: C28 H28 N4 O3
• Name: (3S)-3-[2-(benzenecarbonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-3-(1-ethyl-4-methyl-1H-benzotriazol-5-yl)propanoic acid
• ChEMBL: CHEMBL4642419
• PDB chain: 6typ Chain A Residue 802

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6typ Design, synthesis and identification of novel, orally bioavailable non-covalent Nrf2 activators.
• Resolution: 2.5 Å
• Binding residue (original residue number in PDB): Y334 G364 R415 F478 R483 S508 Y525 S555 A556 Y572 S602 G603
• Binding residue (residue number reindexed from 1): Y9 G39 R90 F153 R158 S183 Y200 S230 A231 Y247 S277 G278
• Annotation score: 1
• Binding affinity: MOAD: Kd=2.7nM
  BindingDB: Kd=2.7nM

External links

• PDB: RCSB:6typ, PDBe:6typ, PDBj:6typ
• PDBsum: 6typ
• PubMed: 31898999
• UniProt: Q14145|KEAP1_HUMAN Kelch-like ECH-associated protein 1 (Gene Name=KEAP1)