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 Tolcapone Ligand Info
Canonical SMILES CC1=CC=C(C=C1)C(=O)C2=CC(=C(C(=C2)O)O)[N+](=O)[O-]
InChI 1S/C14H11NO5/c1-8-2-4-9(5-3-8)13(17)10-6-11(15(19)20)14(18)12(16)7-10/h2-7,16,18H,1H3
InChIKey MIQPIUSUKVNLNT-UHFFFAOYSA-N
PubChem Compound ID 4659569
Drug Binding Sites of Target  Top
PDB ID: 4D7B      Structure of human transthyretin in complex with Tolcapone
Method X-ray diffraction Resolution 1.15 Å Mutation No [1]
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)
SER115
4.671
Residue
Distance (Å)
PDB ID: 5A6I      V122I Transthyretin structure in complex with Tolcalpone
Method X-ray diffraction Resolution 1.86 Å Mutation Yes [1]
PDB Sequence
CPLMVKVLDA
19
VRGSPAINVA
29
VHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGISPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPYSYSTT
119
AVIT
Residue
Distance (Å)
LYS15
3.021
LEU17
3.121
THR106
4.171
ALA108
3.460
ALA109
3.854
Residue
Distance (Å)
LEU110
3.985
SER117
3.413
THR118
3.601
THR119
3.842
VAL121
3.638
PDB ID: 6TXW      V30G Transthyretin structure in complex with Tolcalpone
Method X-ray diffraction Resolution 1.15 Å Mutation Yes [2]
PDB Sequence
CPLMVKVLDA
19
VRGSPAINVA
29
GHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGISPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPYSYSTT
119
AVVTNP
Residue
Distance (Å)
LYS15
2.219
LEU17
2.939
GLU54
4.286
THR106
4.367
ALA108
2.850
ALA109
3.114
Residue
Distance (Å)
LEU110
3.647
SER117
2.101
THR118
3.136
THR119
1.880
VAL121
4.165
PDB ID: 6TXV      A25T Transthyretin structure in complex with Tolcalpone
Method X-ray diffraction Resolution 1.60 Å Mutation Yes [2]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TCW or .TCW2 or .TCW3 or :3TCW;style chemicals stick;color identity;select .A:15 or .A:17 or .A:54 or .A:106 or .A:108 or .A:109 or .A:110 or .A:117 or .A:118 or .A:119 or .A:121; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LYS15
2.724
LEU17
2.797
GLU54
4.941
THR106
4.471
ALA108
2.749
ALA109
3.055
Residue
Distance (Å)
LEU110
3.453
SER117
2.545
THR118
3.131
THR119
3.356
VAL121
3.901
PDB ID: 6XTK      Y114C Transthyretin structure in complex with Tolcalpone
Method X-ray diffraction Resolution 1.70 Å Mutation Yes [2]
PDB Sequence
CPLMVKVLDA
19
VRGSPAINVA
29
VHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGISPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPCSYSTT
119
AVVTNP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TCW or .TCW2 or .TCW3 or :3TCW;style chemicals stick;color identity;select .A:15 or .A:17 or .A:54 or .A:106 or .A:108 or .A:109 or .A:110 or .A:117 or .A:118 or .A:119 or .A:121; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LYS15
2.866
LEU17
3.086
GLU54
4.900
THR106
4.259
ALA108
2.856
ALA109
3.262
Residue
Distance (Å)
LEU110
3.453
SER117
2.207
THR118
3.055
THR119
3.062
VAL121
4.029
References  Top
REF 1 Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity. Nat Commun. 2016 Feb 23;7:10787.
REF 2 Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis. FEBS J. 2021 Jan;288(1):310-324.

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