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 Levothyroxine Ligand Info
Canonical SMILES C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)CC(C(=O)O)N
InChI 1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1
InChIKey XUIIKFGFIJCVMT-LBPRGKRZSA-N
PubChem Compound ID 5819
Drug Binding Sites of Target  Top
PDB ID: 1ETA      THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL 30-->MET VARIANT TO 1.7 ANGSTROMS RESOLUTION
Method X-ray diffraction Resolution 1.70 Å Mutation Yes [1]
PDB Sequence
GPTGTGESKC
10
PLMVKVLDAV
20
RGSPAINVAV
30
HVFRKAADDT
40
WEPFASGKTS
50

ESGELHGLTT
60
EEEFVEGIYK
70
VEIDTKSYWK
80
ALGISPFHEH
90
AEVVFTANDS
100

GPRRYTIAAL
110
LSPYSYSTTA
120
VVTNPKE
Residue
Distance (Å)
LYS15
2.726
VAL16
4.628
LEU17
3.320
GLU54
2.691
THR106
4.074
Residue
Distance (Å)
ALA108
3.638
ALA109
3.125
LEU110
3.357
SER117
4.845
VAL121
4.107
PDB ID: 1ETB      THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL 30-->MET VARIANT TO 1.7 ANGSTROMS RESOLUTION
Method X-ray diffraction Resolution 1.70 Å Mutation No [1]
PDB Sequence
KCPLMVKVLD
18
AVRGSPAINV
28
AVHVFRKAAD
38
DTWEPFASGK
48
TSESGELHGL
58

TTEEEFVEGI
68
YKVEIDTKSY
78
WKALGISPFH
88
EHAEVVFTAN
98
DSGPRRYTIA
108

TLLSPYSYST
118
TAVVTNPK
Residue
Distance (Å)
LYS15
2.636
VAL16
4.804
LEU17
3.628
GLU54
2.695
THR106
4.280
Residue
Distance (Å)
ALA108
3.889
THR109
3.268
LEU110
3.616
VAL121
4.243
PDB ID: 3OZK      Crystal structure of human transthyretin variant A25T in complex with thyroxine (T4)
Method X-ray diffraction Resolution 1.90 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
Residue
Distance (Å)
MET13
4.037
LYS15
2.903
LEU17
3.378
THR106
3.633
ALA108
3.498
ALA109
4.241
Residue
Distance (Å)
LEU110
3.449
SER117
3.014
THR118
3.818
THR119
2.983
VAL121
3.701
PDB ID: 2ROX      TRANSTHYRETIN (ALSO CALLED PREALBUMIN) COMPLEX WITH THYROXINE (T4)
Method X-ray diffraction Resolution 2.00 Å Mutation No [3]
PDB Sequence
CPLMVKVLDA
19
VRGSPAINVA
29
VHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGISPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPYSYSTT
119
AVVTNPKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .T44 or .T442 or .T443 or :3T44;style chemicals stick;color identity;select .A:15 or .A:17 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
3.751
LEU17
3.206
THR106
4.014
ALA108
3.625
ALA109
3.786
Residue
Distance (Å)
LEU110
3.521
SER117
3.936
THR118
4.900
THR119
4.580
VAL121
4.468
PDB ID: 5CR1      Crystal structure of TTR/resveratrol/T4 complex
Method X-ray diffraction Resolution 1.54 Å Mutation Yes [4]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .T44 or .T442 or .T443 or :3T44;style chemicals stick;color identity;select .A:15 or .A:17 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
2.684
LEU17
2.860
THR106
3.506
ALA108
2.696
ALA109
3.216
Residue
Distance (Å)
LEU110
2.165
SER117
4.383
THR118
4.700
THR119
4.368
VAL121
3.313
PDB ID: 1F86      TRANSTHYRETIN THR119MET PROTEIN STABILISATION
Method X-ray diffraction Resolution 1.10 Å Mutation Yes [5]
PDB Sequence
CPLMVKVLDA
19
VRGSPAINVA
29
VHVFRKAADD
39
TWEPFASGKT
49
SESGELHGLT
59

TEEEFVEGIY
69
KVEIDTKSYW
79
KALGISPFHE
89
HAEVVFTAND
99
SGPRRYTIAA
109

LLSPYSYSTM
119
AVVTN
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .T44 or .T442 or .T443 or :3T44;style chemicals stick;color identity;select .A:15 or .A:17 or .A:106 or .A:108 or .A:109 or .A:110 or .A:117 or .A:118 or .A:119; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LYS15
4.027
LEU17
2.826
THR106
4.201
ALA108
3.395
ALA109
3.920
Residue
Distance (Å)
LEU110
3.751
SER117
3.860
THR118
4.569
MET119
4.119
References  Top
REF 1 The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution. J Biol Chem. 1993 Feb 5;268(4):2416-24.
REF 2 Crystal structure of human transthyretin variant A25T in complex with thyroxine (T4)
REF 3 Structures of human transthyretin complexed with thyroxine at 2.0 A resolution and 3',5'-dinitro-N-acetyl-L-thyronine at 2.2 A resolution. Acta Crystallogr D Biol Crystallogr. 1996 Jul 1;52(Pt 4):758-65.
REF 4 Transthyretin Binding Heterogeneity and Anti-amyloidogenic Activity of Natural Polyphenols and Their Metabolites. J Biol Chem. 2015 Dec 11;290(50):29769-80.
REF 5 Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at atomic resolution. J Mol Biol. 2001 Mar 2;306(4):733-44.

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