Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T86462 Target Info
Target Name Transthyretin (TTR)
Synonyms TBPA; Prealbumin; PALB; ATTR
Target Type Successful Target
Gene Name TTR
UniProt ID
TTHY_HUMAN
Ligand General Information  Top
Ligand Name CHF-5074 Ligand Info
Canonical SMILES C1CC1(C2=CC(=C(C=C2)C3=CC(=C(C=C3)Cl)Cl)F)C(=O)O
InChI 1S/C16H11Cl2FO2/c17-12-4-1-9(7-13(12)18)11-3-2-10(8-14(11)19)16(5-6-16)15(20)21/h1-4,7-8H,5-6H2,(H,20,21)
InChIKey LIYLTQQDABRNRX-UHFFFAOYSA-N
PubChem Compound ID 9996409
Drug Binding Sites of Target  Top
PDB ID: 6R6I      Crystal structure of transthyretin mutant A25T in complex with CHF5074, a flurbiprofen analogue
Method X-ray diffraction Resolution 1.47 Å Mutation Yes [1]
PDB Sequence
CPLMVKVLDA
19
VRGSPTINVA
29
VHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGISPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPYSYSTT
119
AVVTNP
Residue
Distance (Å)
LYS15
3.247
LEU17
3.894
GLU54
4.740
THR106
4.890
ALA108
3.661
Residue
Distance (Å)
ALA109
4.267
LEU110
3.894
SER117
3.189
THR118
3.592
THR119
3.954
PDB ID: 4I85      Crystal structure of transthyretin in complex with CHF5074 at neutral pH
Method X-ray diffraction Resolution 1.67 Å Mutation No [2]
PDB Sequence
CPLMVKVLDA
19
VRGSPAINVA
29
VHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGISPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPYSYSTT
119
AVVTNP
Residue
Distance (Å)
LYS15
2.564
LEU17
3.354
GLU54
4.666
ALA108
3.816
ALA109
4.279
Residue
Distance (Å)
LEU110
3.907
SER117
3.419
THR118
3.650
THR119
3.691
PDB ID: 4I87      Crystal structure of TTR variant I84S in complex with CHF5074 at acidic pH
Method X-ray diffraction Resolution 1.69 Å Mutation Yes [2]
PDB Sequence
CPLMVKVLDA
19
VRGSPAINVA
29
VHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGSSPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPYSYSTT
119
AVVTNP
Residue
Distance (Å)
LYS15
3.074
LEU17
3.651
GLU54
4.708
ALA108
3.516
ALA109
3.609
Residue
Distance (Å)
LEU110
3.996
SER117
3.324
THR118
3.747
THR119
3.990
References  Top
REF 1 Structure-activity relationships of flurbiprofen analogues as stabilizers of the amyloidogenic protein transthyretin. J Struct Biol. 2019 Nov 1;208(2):165-173.
REF 2 Structural evidence for native state stabilization of a conformationally labile amyloidogenic transthyretin variant by fibrillogenesis inhibitors. FEBS Lett. 2013 Aug 2;587(15):2325-31.

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