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APR Prediction Models
GAP (Generalized Aggregation Proneness)
ANuPP (Prediciton of Nucleating APRs)
V
L
AmY-Pred (Predicting antibody light chain aggregation)
Aggregation Kinetics Prediction Models
AggreRATE-Disc (Classifying Aggregating Point Mutation)
AggreRATE-Pred (Predicting Aggregation Rate for Point Mutation)
AbsoluRATE (Predicting Absolute aggregation rate)
Amylo-Pipe (Comprehensive aggregation prediction)
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Tutorial
Statistics
Download
Contact Us
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APR Prediction Models:
GAP (Generalized Aggregation Proneness)
ANuPP (Prediciton of Nucleating APRs)
V
L
AmY-Pred (Predicting antibody light chain aggregation)
Aggregation Kinetics Prediction Models:
AggreRATE-Disc (Classifying Aggregating Point Mutation)
AggreRATE-Pred (Predicting Aggregation Rate for Point Mutation)
AbsoluRATE (Predicting Absolute aggregation rate)
Amylo-Pipe (Comprehensive aggregation prediction)
Structure database of aggregation related proteins and peptides
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Protein Name
Peptide Sequence
Entry ID
PDB ID
Method
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Aggregating complex
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Displaying 391 to 420 records out of 565 records fetched.
Entry
PDB ID
Protein
Name
Species
Length
Mutation(s)
Class
Type
Method
Resolution (
Å
)
PMID
S-0391
4TL5
Transthyretin
Homo sapiens
125
S85P
Amyloid
Protein
X-RAY DIFFRACTION
1.44
26459562
S-0392
4TLK
Transthyretin
Homo sapiens
125
S85P/E92P
Amyloid
Protein
X-RAY DIFFRACTION
1.44
26459562
S-0393
4TLS
Transthyretin
Homo sapiens
125
E92P
Amyloid
Protein
X-RAY DIFFRACTION
1.35
26459562
S-0394
4TLT
Transthyretin
Homo sapiens
125
No
Amyloid
Protein
X-RAY DIFFRACTION
1.7
26459562
S-0395
4TM9
Transthyretin
Homo sapiens
125
T119W
Amyloid
Protein
X-RAY DIFFRACTION
1.7
26459562
S-0396
4TNE
Transthyretin
Homo sapiens
125
T119Y
Amyloid
Protein
X-RAY DIFFRACTION
1.55
26459562
S-0397
4TQ8
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.52
26235916
S-0398
4TQH
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.51
26235916
S-0399
4TQI
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.25
26235916
S-0400
4TQP
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.58
26235916
S-0401
4TVK
Acetylcholinesterase
Tetronarce californica
534
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
2.3
25259726
S-0402
4UNT
Immunoglobulin lambda variable 2-8
Homo sapiens
111
Y38E/F99A/F101E
Amyloid
Protein
X-RAY DIFFRACTION
2.7
25138218
S-0403
4UNU
Immunoglobulin lambda variable 2-8
Homo sapiens
111
No
Amyloid
Protein
X-RAY DIFFRACTION
0.95
25138218
S-0404
4UNV
Immunoglobulin lambda variable 2-8
Homo sapiens
111
A45C/F101C
Amyloid
Protein
X-RAY DIFFRACTION
1.6
25138218
S-0405
4XFN
Transthyretin
synthetic construct
6
No
Amyloid
Fibril
X-RAY DIFFRACTION
1.85
26459562
S-0406
4XFO
Transthyretin
synthetic construct
6
No
Amyloid
Fibril
X-RAY DIFFRACTION
1.35
26459562
S-0407
4XXD
Ig kappa chain C region
219 , 223 , 17 , 219 , 223 , 17
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
2.41
25880481
S-0408
4ZNN
Alpha-synuclein
Homo sapiens
10
No
Amyloid
Fibril
ELECTRON CRYSTALLOGRAPHY
1.41
26352473
S-0409
5A6I
Transthyretin
Homo sapiens
128
V122I
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.86
26902880
S-0410
5ACL
Immunoglobulin lambda variable 2-8
Homo sapiens
111
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.49
26576950
S-0411
5ACM
Immunoglobulin lambda variable 2-8
Homo sapiens
111
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.05
26576950
S-0412
5AEF
Amyloid-beta A4 protein
Homo sapiens
28
No
Amyloid
Fibril
ELECTRON MICROSCOPY
5.0
26351699
S-0413
5AKS
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.25
26468275
S-0414
5AKT
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.35
26468275
S-0415
5AKV
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.52
26468275
S-0416
5AL0
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.39
26468275
S-0417
5AL8
Transthyretin
Homo sapiens
127
No
Non-amyloid
Inhibitor complex
X-RAY DIFFRACTION
1.5
26468275
S-0418
5C9K
Amyloid lambda 6 light chain variable region PIP
Homo sapiens
111
R24G
Amyloid
Protein
X-RAY DIFFRACTION
1.92
S-0419
5CFH
Beta-2-microglobulin
Homo sapiens
100
W60G/Y63W
Amyloid
Protein
X-RAY DIFFRACTION
1.49
27150430
S-0420
5CKA
Beta-2-microglobulin
Homo sapiens
100
W60G/N83V
Amyloid
Protein
X-RAY DIFFRACTION
1.7
27150430
Entry:S-0391
PDB ID: 4TL5
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
P
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Chain 2
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
P
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Crystal Structure of Human Transthyretin Ser85Pro Mutant
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
125
Species:
Homo sapiens
Mutation(s):
S85P
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TL5
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.44
R free:
0.198
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
nan
A
Na 1
22.99
SODIUM ION
[Na+]
FKNQFGJONOIPTF-UHFFFAOYSA-N
CL
B
Cl -1
35.45
CHLORIDE ION
[Cl-]
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Entry:S-0392
PDB ID: 4TLK
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
P
P
F
H
E
H
A
P
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Chain 2
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
P
P
F
H
E
H
A
P
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Crystal Structure of Human Transthyretin Ser85Pro/Glu92Pro Mutant
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
125
Species:
Homo sapiens
Mutation(s):
S85P/E92P
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TLK
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.44
R free:
0.201
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
nan
A
Na 1
22.99
SODIUM ION
[Na+]
FKNQFGJONOIPTF-UHFFFAOYSA-N
GOL
B
C3 H8 O3
92.09
GLYCEROL
C(C(CO)O)O
PEDCQBHIVMGVHV-UHFFFAOYSA-N
nan
B
Na 1
22.99
SODIUM ION
[Na+]
FKNQFGJONOIPTF-UHFFFAOYSA-N
PEG
B
C4 H10 O3
106.12
DI(HYDROXYETHYL)ETHER
C(COCCO)O
MTHSVFCYNBDYFN-UHFFFAOYSA-N
Entry:S-0393
PDB ID: 4TLS
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
P
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Chain 2
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
P
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Crystal Structure of Human Transthyretin Glu92Pro Mutant
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
125
Species:
Homo sapiens
Mutation(s):
E92P
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TLS
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.35
R free:
0.192
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
GOL
A
C3 H8 O3
92.09
GLYCEROL
C(C(CO)O)O
PEDCQBHIVMGVHV-UHFFFAOYSA-N
PO4
A
O4 P -3
94.97
PHOSPHATE ION
[O-]P(=O)([O-])[O-]
NBIIXXVUZAFLBC-UHFFFAOYSA-K
nan
B
Na 1
22.99
SODIUM ION
[Na+]
FKNQFGJONOIPTF-UHFFFAOYSA-N
PO4
B
O4 P -3
94.97
PHOSPHATE ION
[O-]P(=O)([O-])[O-]
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Entry:S-0394
PDB ID: 4TLT
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Chain 2
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Crystal structure of human transthyretin
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
Download
Entry:
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JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
125
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TLT
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.7
R free:
0.23199999
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
MG
A
Mg 2
24.31
MAGNESIUM ION
[Mg+2]
JLVVSXFLKOJNIY-UHFFFAOYSA-N
OCS
A
C3 H7 N O5 S
169.16
CYSTEINESULFONIC ACID
C([C@@H](C(=O)O)N)S(=O)(=O)O
XVOYSCVBGLVSOL-REOHCLBHSA-N
MG
B
Mg 2
24.31
MAGNESIUM ION
[Mg+2]
JLVVSXFLKOJNIY-UHFFFAOYSA-N
OCS
B
C3 H7 N O5 S
169.16
CYSTEINESULFONIC ACID
C([C@@H](C(=O)O)N)S(=O)(=O)O
XVOYSCVBGLVSOL-REOHCLBHSA-N
Entry:S-0395
PDB ID: 4TM9
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
W
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Chain 2
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
W
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Crystal Structure of Human Transthyretin Thr119Trp Mutant
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
125
Species:
Homo sapiens
Mutation(s):
T119W
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TM9
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.7
R free:
0.184
Entry:S-0396
PDB ID: 4TNE
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
Y
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Chain 2
1
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
I
N
V
A
V
H
V
F
25
26
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
E
S
G
E
L
H
G
L
50
51
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
K
S
Y
W
K
A
L
G
75
76
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
G
P
R
R
Y
T
I
A
100
101
A
L
L
S
P
Y
S
Y
S
T
Y
A
V
V
T
N
P
K
E
H
H
H
H
H
H
125
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Crystal Structure of Human Transthyretin Thr119Tyr Mutant
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
125
Species:
Homo sapiens
Mutation(s):
T119Y
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TNE
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.55
R free:
0.201
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
GOL
B
C3 H8 O3
92.09
GLYCEROL
C(C(CO)O)O
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Entry:S-0397
PDB ID: 4TQ8
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Dual binding mode for 3-(9H-fluoren-9-ylideneaminooxy)propanoic acid binding to Human transthyretin (TTR)
The use of polyethylene glycol (PEG) has been evaluated as an alternative to obtain new TTR complexes with (R)-3-(9-fluoren-9-ylideneaminooxy)-2-methyl-N-(methylsulfonyl) propionamide (48R(1)) and 2-(9H-fluoren-9-ylideneaminooxy) acetic acid (ES8(2)). The previously described fluorenyl based inhibitors (S)-3-((9H-fluoren-9-ylideneamino)oxy)-2-methylpropanoic acid (6BD) and 3-((9H-fluoren-9-ylideneamino)oxy)propanoic acid (7BD) have been re-evaluated with the changed crystallization method.
Literature
PMID:
26235916
Author(s):
Ciccone, L., Nencetti, S., Rossello, A., Tepshi, L., Stura, E.A., Orlandini, E.
Reference:
J Enzyme Inhib Med Chem. 2016 Oct;31(5):824-33.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TQ8
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
HORMONE
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.52
R free:
0.21
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
7BD
A
C16 H13 N O3
267.28
3-[(9H-fluoren-9-ylideneamino)oxy]propanoic acid
c1ccc2c(c1)-c3ccccc3C2=NOCCC(=O)O
LASWLEUVWJDDBA-UHFFFAOYSA-N
7BD
B
C16 H13 N O3
267.28
3-[(9H-fluoren-9-ylideneamino)oxy]propanoic acid
c1ccc2c(c1)-c3ccccc3C2=NOCCC(=O)O
LASWLEUVWJDDBA-UHFFFAOYSA-N
EDO
B
C2 H6 O2
62.07
1,2-ETHANEDIOL
C(CO)O
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Entry:S-0398
PDB ID: 4TQH
CSV
JSON
Close ×
Structure
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View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Human transthyretin (TTR) complexed with 3-(9H-fluoren-9-ylideneaminooxy)ethanoic acid
The use of polyethylene glycol (PEG) has been evaluated as an alternative to obtain new TTR complexes with (R)-3-(9-fluoren-9-ylideneaminooxy)-2-methyl-N-(methylsulfonyl) propionamide (48R(1)) and 2-(9H-fluoren-9-ylideneaminooxy) acetic acid (ES8(2)). The previously described fluorenyl based inhibitors (S)-3-((9H-fluoren-9-ylideneamino)oxy)-2-methylpropanoic acid (6BD) and 3-((9H-fluoren-9-ylideneamino)oxy)propanoic acid (7BD) have been re-evaluated with the changed crystallization method.
Literature
PMID:
26235916
Author(s):
Ciccone, L., Nencetti, S., Rossello, A., Tepshi, L., Stura, E.A., Orlandini, E.
Reference:
J Enzyme Inhib Med Chem. 2016 Oct;31(5):824-33.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TQH
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
HORMONE
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.51
R free:
0.222
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
EDO
A
C2 H6 O2
62.07
1,2-ETHANEDIOL
C(CO)O
LYCAIKOWRPUZTN-UHFFFAOYSA-N
ES8
A
C15 H11 N O3
253.25
[(9H-fluoren-9-ylideneamino)oxy]acetic acid
c1ccc2c(c1)-c3ccccc3C2=NOCC(=O)O
PLACMAVVPYGZGF-UHFFFAOYSA-N
ES8
B
C15 H11 N O3
253.25
[(9H-fluoren-9-ylideneamino)oxy]acetic acid
c1ccc2c(c1)-c3ccccc3C2=NOCC(=O)O
PLACMAVVPYGZGF-UHFFFAOYSA-N
Entry:S-0399
PDB ID: 4TQI
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Human transthyretin (TTR) complexed with 3-(9H-fluoren-9-ylideneaminooxy)propanoic acid in a dual binding mode
The use of polyethylene glycol (PEG) has been evaluated as an alternative to obtain new TTR complexes with (R)-3-(9-fluoren-9-ylideneaminooxy)-2-methyl-N-(methylsulfonyl) propionamide (48R(1)) and 2-(9H-fluoren-9-ylideneaminooxy) acetic acid (ES8(2)). The previously described fluorenyl based inhibitors (S)-3-((9H-fluoren-9-ylideneamino)oxy)-2-methylpropanoic acid (6BD) and 3-((9H-fluoren-9-ylideneamino)oxy)propanoic acid (7BD) have been re-evaluated with the changed crystallization method.
Literature
PMID:
26235916
Author(s):
Ciccone, L., Nencetti, S., Rossello, A., Tepshi, L., Stura, E.A., Orlandini, E.
Reference:
J Enzyme Inhib Med Chem. 2016 Oct;31(5):824-33.
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Entry:
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Structure:
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CIF
FASTA
Contact Network:
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Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TQI
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.25
R free:
0.20800000
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
6BD
A
C17 H15 N O3
281.31
(2S)-3-[(9H-fluoren-9-ylideneamino)oxy]-2-methylpropanoic acid
C[C@@H](CON=C1c2ccccc2-c3c1cccc3)C(=O)O
ZHFDVDMCVXUGGF-NSHDSACASA-N
6BD
B
C17 H15 N O3
281.31
(2S)-3-[(9H-fluoren-9-ylideneamino)oxy]-2-methylpropanoic acid
C[C@@H](CON=C1c2ccccc2-c3c1cccc3)C(=O)O
ZHFDVDMCVXUGGF-NSHDSACASA-N
GOL
B
C3 H8 O3
92.09
GLYCEROL
C(C(CO)O)O
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Entry:S-0400
PDB ID: 4TQP
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Structure
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Human transthyretin (TTR) complexed with (R)-3-(9H-fluoren-9-ylideneaminooxy)-2-methyl-N-(methylsulfonyl) propionamide in a dual binding mode
The use of polyethylene glycol (PEG) has been evaluated as an alternative to obtain new TTR complexes with (R)-3-(9-fluoren-9-ylideneaminooxy)-2-methyl-N-(methylsulfonyl) propionamide (48R(1)) and 2-(9H-fluoren-9-ylideneaminooxy) acetic acid (ES8(2)). The previously described fluorenyl based inhibitors (S)-3-((9H-fluoren-9-ylideneamino)oxy)-2-methylpropanoic acid (6BD) and 3-((9H-fluoren-9-ylideneamino)oxy)propanoic acid (7BD) have been re-evaluated with the changed crystallization method.
Literature
PMID:
26235916
Author(s):
Ciccone, L., Nencetti, S., Rossello, A., Tepshi, L., Stura, E.A., Orlandini, E.
Reference:
J Enzyme Inhib Med Chem. 2016 Oct;31(5):824-33.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
Transthyretin
Structure Information
PDB ID:
4TQP
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
HORMONE
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.58
R free:
0.198
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
48R
A
C18 H18 N2 O4 S
358.41
(2R)-3-[(9H-fluoren-9-ylideneamino)oxy]-2-methyl-N-(methylsulfonyl)propanamide
C[C@H](CON=C1c2ccccc2-c3c1cccc3)C(=O)NS(=O)(=O)C
FRTXAYQPEDIBAD-GFCCVEGCSA-N
GOL
A
C3 H8 O3
92.09
GLYCEROL
C(C(CO)O)O
PEDCQBHIVMGVHV-UHFFFAOYSA-N
48R
B
C18 H18 N2 O4 S
358.41
(2R)-3-[(9H-fluoren-9-ylideneamino)oxy]-2-methyl-N-(methylsulfonyl)propanamide
C[C@H](CON=C1c2ccccc2-c3c1cccc3)C(=O)NS(=O)(=O)C
FRTXAYQPEDIBAD-GFCCVEGCSA-N
GOL
B
C3 H8 O3
92.09
GLYCEROL
C(C(CO)O)O
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Entry:S-0401
PDB ID: 4TVK
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Structure
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Sequence & Sec. Str.
Chain 1
1
D
H
S
E
L
L
V
N
T
K
S
G
K
V
M
G
T
R
V
P
V
L
S
S
H
25
26
I
S
A
F
L
G
I
P
F
A
E
P
P
V
G
N
M
R
F
R
R
P
E
P
K
50
51
K
P
W
S
G
V
W
N
A
S
T
Y
P
N
N
C
Q
Q
Y
V
D
E
Q
F
P
75
76
G
F
S
G
S
E
M
W
N
P
N
R
E
M
S
E
D
C
L
Y
L
N
I
W
V
100
101
P
S
P
R
P
K
S
T
T
V
M
V
W
I
Y
G
G
G
F
Y
S
G
S
S
T
125
126
L
D
V
Y
N
G
K
Y
L
A
Y
T
E
E
V
V
L
V
S
L
S
Y
R
V
G
150
151
A
F
G
F
L
A
L
H
G
S
Q
E
A
P
G
N
V
G
L
L
D
Q
R
M
A
175
176
L
Q
W
V
H
D
N
I
Q
F
F
G
G
D
P
K
T
V
T
I
F
G
E
S
A
200
201
G
G
A
S
V
G
M
H
I
L
S
P
G
S
R
D
L
F
R
R
A
I
L
Q
S
225
226
G
S
P
N
C
P
W
A
S
V
S
V
A
E
G
R
R
R
A
V
E
L
G
R
N
250
251
L
N
C
N
L
N
S
D
E
E
L
I
H
C
L
R
E
K
K
P
Q
E
L
I
D
275
276
V
E
W
N
V
L
P
F
D
S
I
F
R
F
S
F
V
P
V
I
D
G
E
F
F
300
301
P
T
S
L
E
S
M
L
N
S
G
N
F
K
K
T
Q
I
L
L
G
V
N
K
D
325
326
E
G
S
F
F
L
L
Y
G
A
P
G
F
S
K
D
S
E
S
K
I
S
R
E
D
350
351
F
M
S
G
V
K
L
S
V
P
H
A
N
D
L
G
L
D
A
V
T
L
Q
Y
T
375
376
D
W
M
D
D
N
N
G
I
K
N
R
D
G
L
D
D
I
V
G
D
H
N
V
I
400
401
C
P
L
M
H
F
V
N
K
Y
T
K
F
G
N
G
T
Y
L
Y
F
F
N
H
R
425
426
A
S
N
L
V
W
P
E
W
M
G
V
I
H
G
Y
E
I
E
F
V
F
G
L
P
450
451
L
V
K
E
L
N
Y
T
A
E
E
E
A
L
S
R
R
I
M
H
Y
W
A
T
F
475
476
A
K
T
G
N
P
N
E
P
H
S
Q
E
S
K
W
P
L
F
T
T
K
E
Q
K
500
501
F
I
D
L
N
T
E
P
M
K
V
H
Q
R
L
R
V
Q
M
C
V
F
W
N
Q
525
526
F
L
P
K
L
L
N
A
T
534
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A CHLOROTACRINE-JUGLONE HYBRID INHIBITOR
They report the identification of multitarget anti-Alzheimer compounds designed by combining a naphthoquinone function and a tacrine fragment. In vitro, 15 compounds displayed excellent acetylcholinesterase (AChE) inhibitory potencies and interesting capabilities to block amyloid-Beta (ABeta) aggregation. The X-ray analysis of one of those compounds in complex with AChE allowed rationalizing the outstanding activity data.
Literature
PMID:
25259726
Author(s):
Nepovimova, E., Uliassi, E., Korabecny, J., Pena-Altamira, L.E., Samez, S., Pesaresi, A., Garcia, G.E., Bartolini, M., Andrisano, V., Bergamini, C., Fato, R., Lamba, D., Roberti, M., Kuca, K., Monti, B., Bolognesi, M.L.
Reference:
J Med Chem. 2014 Oct 23;57(20):8576-89.
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Entry:
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Structure:
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Contact Network:
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Protein Information
Protein Name:
Acetylcholinesterase
Alternative Name:
Gene Name:
ache
Sequence Length:
534
Species:
Tetronarce californica
Mutation(s):
No
E.C. Number:
3.1.1.7
UniProt ID:
P04058
Keyword(s):
Acetylcholinesterase
Structure Information
PDB ID:
4TVK
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Monomer - A
PDB Classification:
HYDROLASE
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
2.3
R free:
0.225
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
NAG
A
C8 H15 N O6
221.21
N-ACETYL-D-GLUCOSAMINE
CC(=O)N[C@@H]1[C@H]([C@@H]([C@H](O[C@H]1O)CO)O)O
OVRNDRQMDRJTHS-FMDGEEDCSA-N
TJH
A
C25 H22 Cl N3 O3
447.91
2-({2-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]ethyl}amino)-5-hydroxynaphthalene-1,4-dione
c1cc2c(c(c1)O)C(=O)C=C(C2=O)NCCNc3c4ccc(cc4nc5c3CCCC5)Cl
QOYHHKMVCBONOU-UHFFFAOYSA-N
Entry:S-0402
PDB ID: 4UNT
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Sequence & Sec. Str.
Chain 1
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Chain 2
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Chain 3
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Chain 4
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Chain 5
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Chain 6
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Chain 7
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Chain 8
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
E
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
A
100
101
V
E
G
T
G
T
K
V
T
V
L
111
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Induced monomer of the Mcg variable domain; Formation of Amyloid Fibers by Monomeric Light-Chain Variable Domains.
They identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers.
Literature
PMID:
25138218
Author(s):
Brumshtein, B., Esswein, S.R., Landau, M., Ryan, C.M., Whitelegge, J.P., Phillips, M.L., Cascio, D., Sawaya, M.R., Eisenberg, D.S.
Reference:
J Biol Chem. 2014 Oct 3;289(40):27513-25.
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Entry:
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Structure:
PDB
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FASTA
Contact Network:
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JSON
Protein Information
Protein Name:
Immunoglobulin lambda variable 2-8
Alternative Name:
Ig lambda chain V-II region BO, Ig lambda chain V-II region MGC
Gene Name:
IGLV2-8
Sequence Length:
111
Species:
Homo sapiens
Mutation(s):
Y38E/F99A/F101E
E.C. Number:
UniProt ID:
P01709
Keyword(s):
IG LAMBDA CHAIN V-II REGION MGC
Structure Information
PDB ID:
4UNT
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 8-mer - A8
PDB Classification:
IMMUNE SYSTEM
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
2.7
R free:
0.289
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
SO4
A
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
SO4
C
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
SO4
D
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
SO4
E
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
SO4
F
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
SO4
H
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
Entry:S-0403
PDB ID: 4UNU
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Structure
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
Y
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
F
100
101
V
F
G
T
G
T
K
V
T
V
L
111
Chain 2
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
Y
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
F
100
101
V
F
G
T
G
T
K
V
T
V
L
111
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
MCG - a dimer of lambda variable domains
They identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers.
Literature
PMID:
25138218
Author(s):
Brumshtein, B., Esswein, S.R., Landau, M., Ryan, C.M., Whitelegge, J.P., Phillips, M.L., Cascio, D., Sawaya, M.R., Eisenberg, D.S.
Reference:
J Biol Chem. 2014 Oct 3;289(40):27513-25.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Immunoglobulin lambda variable 2-8
Alternative Name:
Ig lambda chain V-II region BO, Ig lambda chain V-II region MGC
Gene Name:
IGLV2-8
Sequence Length:
111
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P01709
Keyword(s):
IG LAMBDA CHAIN V-II REGION MGC
Structure Information
PDB ID:
4UNU
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 2-mer - A2
PDB Classification:
IMMUNE SYSTEM
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
0.95
R free:
0.13
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
15P
A
C69 H140 O35
1529.83
POLYETHYLENE GLYCOL (N=34)
COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO
VUYXVWGKCKTUMF-UHFFFAOYSA-N
SO4
B
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
Entry:S-0404
PDB ID: 4UNV
CSV
JSON
Close ×
Structure
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
Y
Q
Q
H
A
G
K
C
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
F
100
101
V
C
G
T
G
T
K
V
T
V
L
111
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Covalent dimer of lambda variable domains
They identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers.
Literature
PMID:
25138218
Author(s):
Brumshtein, B., Esswein, S.R., Landau, M., Ryan, C.M., Whitelegge, J.P., Phillips, M.L., Cascio, D., Sawaya, M.R., Eisenberg, D.S.
Reference:
J Biol Chem. 2014 Oct 3;289(40):27513-25.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Immunoglobulin lambda variable 2-8
Alternative Name:
Ig lambda chain V-II region BO, Ig lambda chain V-II region MGC
Gene Name:
IGLV2-8
Sequence Length:
111
Species:
Homo sapiens
Mutation(s):
A45C/F101C
E.C. Number:
UniProt ID:
P01709
Keyword(s):
IG LAMBDA CHAIN V-II REGION MGC
Structure Information
PDB ID:
4UNV
Amyloid Category:
Amyloid
Type:
Protein
Global Stoichiometry:
Homo 2-mer - A2
PDB Classification:
IMMUNE SYSTEM
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.6
R free:
0.258
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
SO4
A
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
Entry:S-0405
PDB ID: 4XFN
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
A
E
V
V
F
T
6
Chain 2
1
A
E
V
V
F
T
6
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Structure of an Amyloid forming peptide AEVVFT from Human Transthyretin
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
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Entry:
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Structure:
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FASTA
Contact Network:
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Protein Information
Protein Name:
Transthyretin
Alternative Name:
Gene Name:
Sequence Length:
6
Species:
synthetic construct
Mutation(s):
No
E.C. Number:
UniProt ID:
Keyword(s):
Amyloid forming peptide AEVVFT
Structure Information
PDB ID:
4XFN
Amyloid Category:
Amyloid
Type:
Fibril
Global Stoichiometry:
Homo 8-mer - A8
PDB Classification:
PROTEIN FIBRIL
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.85
R free:
0.201
Entry:S-0406
PDB ID: 4XFO
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Sequence & Sec. Str.
Chain 1
1
T
A
V
V
T
N
6
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Structure of an amyloid-forming segment TAVVTN from human Transthyretin
They identify Beta-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, they designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.
Literature
PMID:
26459562
Author(s):
Saelices, L., Johnson, L.M., Liang, W.Y., Sawaya, M.R., Cascio, D., Ruchala, P., Whitelegge, J., Jiang, L., Riek, R., Eisenberg, D.S.
Reference:
J Biol Chem. 2015 Nov 27;290(48):28932-43.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
Gene Name:
Sequence Length:
6
Species:
synthetic construct
Mutation(s):
No
E.C. Number:
UniProt ID:
Keyword(s):
Amyloid-forming peptide TAVVTN
Structure Information
PDB ID:
4XFO
Amyloid Category:
Amyloid
Type:
Fibril
Global Stoichiometry:
PDB Classification:
PROTEIN FIBRIL
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.35
R free:
0.14800000
Entry:S-0407
PDB ID: 4XXD
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JSON
Close ×
Structure
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
D
V
V
M
T
Q
S
P
L
S
L
P
V
T
L
G
Q
P
A
S
I
S
C
R
S
25
26
S
Q
S
L
I
Y
S
D
G
N
A
Y
L
H
W
F
L
Q
K
P
G
Q
S
P
R
50
51
L
L
I
Y
K
V
S
N
R
F
S
G
V
P
D
R
F
S
G
S
G
S
G
T
D
75
76
F
T
L
K
I
S
R
V
E
A
E
D
V
G
V
Y
Y
C
S
Q
S
T
H
V
P
100
101
W
T
F
G
Q
G
T
K
V
E
I
K
R
T
V
A
A
P
S
V
F
I
F
P
P
125
126
S
D
E
Q
L
K
S
G
T
A
S
V
V
C
L
L
N
N
F
Y
P
R
E
A
K
150
151
V
Q
W
K
V
D
N
A
L
Q
S
G
N
S
Q
E
S
V
T
E
Q
D
S
K
D
175
176
S
T
Y
S
L
S
S
T
L
T
L
S
K
A
D
Y
E
K
H
K
V
Y
A
C
E
200
201
V
T
H
Q
G
L
S
S
P
V
T
K
S
F
N
R
G
E
C
219
Chain 2
1
E
V
Q
L
V
E
S
G
G
G
L
V
Q
P
G
G
S
L
R
L
S
C
A
A
S
25
26
G
F
T
F
S
R
Y
S
M
S
W
V
R
Q
A
P
G
K
G
L
E
L
V
A
Q
50
51
I
N
S
V
G
S
S
T
Y
Y
P
D
T
V
K
G
R
F
T
I
S
R
D
N
A
75
76
K
N
T
L
Y
L
Q
M
N
S
L
R
A
E
D
T
A
V
Y
Y
C
A
S
G
D
100
101
Y
W
G
Q
G
T
L
V
T
V
S
S
A
S
T
K
G
P
S
V
F
P
L
A
P
125
126
S
S
K
S
T
S
G
G
T
A
A
L
G
C
L
V
K
D
Y
F
P
E
P
V
T
150
151
V
S
W
N
S
G
A
L
T
S
G
V
H
T
F
P
A
V
L
Q
S
S
G
L
Y
175
176
S
L
S
S
V
V
T
V
P
S
S
S
L
G
T
Q
T
Y
I
C
N
V
N
H
K
200
201
P
S
N
T
K
V
D
K
K
V
E
P
K
S
C
H
H
H
H
H
H
H
H
223
Chain 3
1
V
H
H
Q
K
L
V
F
F
A
E
D
V
G
S
N
K
17
Chain 4
1
D
V
V
M
T
Q
S
P
L
S
L
P
V
T
L
G
Q
P
A
S
I
S
C
R
S
25
26
S
Q
S
L
I
Y
S
D
G
N
A
Y
L
H
W
F
L
Q
K
P
G
Q
S
P
R
50
51
L
L
I
Y
K
V
S
N
R
F
S
G
V
P
D
R
F
S
G
S
G
S
G
T
D
75
76
F
T
L
K
I
S
R
V
E
A
E
D
V
G
V
Y
Y
C
S
Q
S
T
H
V
P
100
101
W
T
F
G
Q
G
T
K
V
E
I
K
R
T
V
A
A
P
S
V
F
I
F
P
P
125
126
S
D
E
Q
L
K
S
G
T
A
S
V
V
C
L
L
N
N
F
Y
P
R
E
A
K
150
151
V
Q
W
K
V
D
N
A
L
Q
S
G
N
S
Q
E
S
V
T
E
Q
D
S
K
D
175
176
S
T
Y
S
L
S
S
T
L
T
L
S
K
A
D
Y
E
K
H
K
V
Y
A
C
E
200
201
V
T
H
Q
G
L
S
S
P
V
T
K
S
F
N
R
G
E
C
219
Chain 5
1
E
V
Q
L
V
E
S
G
G
G
L
V
Q
P
G
G
S
L
R
L
S
C
A
A
S
25
26
G
F
T
F
S
R
Y
S
M
S
W
V
R
Q
A
P
G
K
G
L
E
L
V
A
Q
50
51
I
N
S
V
G
S
S
T
Y
Y
P
D
T
V
K
G
R
F
T
I
S
R
D
N
A
75
76
K
N
T
L
Y
L
Q
M
N
S
L
R
A
E
D
T
A
V
Y
Y
C
A
S
G
D
100
101
Y
W
G
Q
G
T
L
V
T
V
S
S
A
S
T
K
G
P
S
V
F
P
L
A
P
125
126
S
S
K
S
T
S
G
G
T
A
A
L
G
C
L
V
K
D
Y
F
P
E
P
V
T
150
151
V
S
W
N
S
G
A
L
T
S
G
V
H
T
F
P
A
V
L
Q
S
S
G
L
Y
175
176
S
L
S
S
V
V
T
V
P
S
S
S
L
G
T
Q
T
Y
I
C
N
V
N
H
K
200
201
P
S
N
T
K
V
D
K
K
V
E
P
K
S
C
H
H
H
H
H
H
H
H
223
Chain 6
1
V
H
H
Q
K
L
V
F
F
A
E
D
V
G
S
N
K
17
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Crystal Structure of mid-region amyloid beta capture by solanezumab
Solanezumab (Eli Lilly) and crenezumab (Genentech) are the leading clinical antibodies targeting Amyloid-Beta (ABeta) to be tested in multiple Phase III clinical trials for the prevention of Alzheimer's disease in at-risk individuals. ABeta capture by these clinical antibodies is explained here with the first reported mid-region ABeta-anti-ABeta complex crystal structure. Solanezumab accommodates a large ABeta epitope (buried interface over residues 16 to 26) that forms extensive contacts and hydrogen bonds to the antibody, largely via main-chain ABeta atoms and a deeply buried Phe19-Phe20 dipeptide core. The conformation of ABeta captured is an intermediate between observed sheet and helical forms with intramolecular hydrogen bonds stabilising residues 20-26 in a helical conformation.
Literature
PMID:
25880481
Author(s):
Crespi, G.A., Hermans, S.J., Parker, M.W., Miles, L.A.
Reference:
Sci Rep. 2015 Apr 16;5:9649.
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Protein Information
Protein Name:
Ig kappa chain C region
Alternative Name:
Ig kappa chain C region, Ig kappa chain C region AG, Ig kappa chain C region CUM, Ig kappa chain C region EU, Ig kappa chain C region OU, Ig kappa chain C region ROY, Ig kappa chain C region TI & Ig gamma-1 chain C region, Ig gamma-1 chain C region EU, Ig
Gene Name:
IGKC & IGHG1 & APP, A4, AD1 & IGKC & IGHG1 & APP, A4, AD1
Sequence Length:
219 , 223 , 17 , 219 , 223 , 17
Species:
Mutation(s):
No
E.C. Number:
UniProt ID:
Keyword(s):
Structure Information
PDB ID:
4XXD
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Hetero 2-mer - AB
PDB Classification:
IMMUNE SYSTEM
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
2.41
R free:
0.29
Entry:S-0408
PDB ID: 4ZNN
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Sequence & Sec. Str.
Chain 1
1
G
V
V
H
G
V
T
T
V
A
10
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
MicroED structure of the segment, GVVHGVTTVA, from the A53T familial mutant of Parkinson's disease protein, alpha-synuclein residues 47-56
An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human Alpha-synuclein. The structure exhibits protofibrils built of pairs of face-to-face Beta-sheets. X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length Alpha-synuclein. The NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length Alpha-synuclein fibril, presenting opportunities for the design of inhibitors of Alpha-synuclein fibrils.
Literature
PMID:
26352473
Author(s):
Rodriguez, J.A., Ivanova, M.I., Sawaya, M.R., Cascio, D., Reyes, F.E., Shi, D., Sangwan, S., Guenther, E.L., Johnson, L.M., Zhang, M., Jiang, L., Arbing, M.A., Nannenga, B.L., Hattne, J., Whitelegge, J., Brewster, A.S., Messerschmidt, M., Boutet, S., Saut
Reference:
Nature. 2015 Sep 24;525(7570):486-90.
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Protein Information
Protein Name:
Alpha-synuclein
Alternative Name:
Gene Name:
Sequence Length:
10
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P37840
Keyword(s):
Alpha-synuclein
Structure Information
PDB ID:
4ZNN
Amyloid Category:
Amyloid
Type:
Fibril
Global Stoichiometry:
Homo 10-mer - A10
PDB Classification:
LIPID BINDING PROTEIN
Method:
ELECTRON CRYSTALLOGRAPHY
Resolution (
Å
):
1.41
R free:
0.282
Entry:S-0409
PDB ID: 5A6I
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
M
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
25
26
A
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
50
51
S
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
75
76
T
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
100
101
S
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
I
T
N
125
126
P
K
E
128
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
V122I Transthyretin structure in complex with Tolcalpone
Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis.
Literature
PMID:
26902880
Author(s):
Reverter, D., Gallego, P., Santana, R., Ventura, S.
Reference:
Nat Commun. 2016 Feb 23;7:10787.
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Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
128
Species:
Homo sapiens
Mutation(s):
V122I
E.C. Number:
UniProt ID:
P02766
Keyword(s):
TRANSTHYRETIN
Structure Information
PDB ID:
5A6I
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.86
R free:
0.271
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
TCW
A
C14 H11 N O5
273.24
Tolcapone
Cc1ccc(cc1)C(=O)c2cc(c(c(c2)O)O)[N+](=O)[O-]
MIQPIUSUKVNLNT-UHFFFAOYSA-N
Entry:S-0410
PDB ID: 5ACL
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
Y
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
F
100
101
V
F
G
T
G
T
K
V
T
V
L
111
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Mcg immunoglobulin variable domain with sulfasalazine
Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. They identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer.
Literature
PMID:
26576950
Author(s):
Brumshtein, B., Esswein, S.R., Salwinski, L., Phillips, M.L., Ly, A.T., Cascio, D., Sawaya, M.R., Eisenberg, D.S.
Reference:
Elife. 2015 Nov 18;4:e10935.
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Protein Information
Protein Name:
Immunoglobulin lambda variable 2-8
Alternative Name:
Ig lambda chain V-II region BO, Ig lambda chain V-II region MGC
Gene Name:
IGLV2-8
Sequence Length:
111
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P01709
Keyword(s):
MCG
Structure Information
PDB ID:
5ACL
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Monomer - A
PDB Classification:
IMMUNE SYSTEM
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.49
R free:
0.187
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
SAS
A
C18 H14 N4 O5 S
398.39
2-HYDROXY-(5-([4-(2-PYRIDINYLAMINO)SULFONYL]PHENYL)AZO)BENZOIC ACID
c1ccnc(c1)NS(=O)(=O)c2ccc(cc2)/N=N/c3ccc(c(c3)C(=O)O)O
NCEXYHBECQHGNR-QZQOTICOSA-N
SO4
A
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
Entry:S-0411
PDB ID: 5ACM
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Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
Y
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
F
100
101
V
F
G
T
G
T
K
V
T
V
L
111
Chain 2
1
G
Q
S
A
L
T
Q
P
P
S
A
S
G
S
L
G
Q
S
V
T
I
S
C
T
G
25
26
T
S
S
D
V
G
G
Y
N
Y
V
S
W
Y
Q
Q
H
A
G
K
A
P
K
V
I
50
51
I
Y
E
V
N
K
R
P
S
G
V
P
D
R
F
S
G
S
K
S
G
N
T
A
S
75
76
L
T
V
S
G
L
Q
A
E
D
E
A
D
Y
Y
C
S
S
Y
E
G
S
D
N
F
100
101
V
F
G
T
G
T
K
V
T
V
L
111
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Mcg immunoglobulin variable domain with methylene blue
Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. They identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer.
Literature
PMID:
26576950
Author(s):
Brumshtein, B., Esswein, S.R., Salwinski, L., Phillips, M.L., Ly, A.T., Cascio, D., Sawaya, M.R., Eisenberg, D.S.
Reference:
Elife. 2015 Nov 18;4:e10935.
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Protein Information
Protein Name:
Immunoglobulin lambda variable 2-8
Alternative Name:
Ig lambda chain V-II region BO, Ig lambda chain V-II region MGC
Gene Name:
IGLV2-8
Sequence Length:
111
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P01709
Keyword(s):
MCG
Structure Information
PDB ID:
5ACM
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Monomer - A
PDB Classification:
IMMUNE SYSTEM
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.05
R free:
0.122
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
MBT
A
C16 H18 N3 S 1
284.4
3,7-BIS(DIMETHYLAMINO)PHENOTHIAZIN-5-IUM
CN(C)c1ccc2c(c1)[s+]c3cc(ccc3n2)N(C)C
RBTBFTRPCNLSDE-UHFFFAOYSA-N
SO4
A
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
B
C3 H8 O3
92.09
GLYCEROL
C(C(CO)O)O
PEDCQBHIVMGVHV-UHFFFAOYSA-N
SO4
B
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
Entry:S-0412
PDB ID: 5AEF
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Sequence & Sec. Str.
Chain 1
1
Q
K
L
V
F
F
A
E
D
V
G
S
N
K
G
A
I
I
G
L
M
V
G
G
V
25
26
V
I
A
28
Chain 2
1
Q
K
L
V
F
F
A
E
D
V
G
S
N
K
G
A
I
I
G
L
M
V
G
G
V
25
26
V
I
A
28
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Electron cryo-microscopy of an Abeta(1-42)amyloid fibril
They combined electron cryomicroscopy, 3D reconstruction, and integrative structural modeling methods to determine the molecular architecture of a fibril formed by ABeta(1-42), a particularly pathogenic variant of ABeta peptide. Our model reveals that the individual layers of the ABeta fibril are formed by peptide dimers with face-to-face packing. The two peptides forming the dimer possess identical tilde-shaped conformations and interact with each other by packing of their hydrophobic C-terminal Beta-strands. The peptide C termini are located close to the main fibril axis, where they produce a hydrophobic core and are surrounded by the structurally more flexible and charged segments of the peptide N termini.
Literature
PMID:
26351699
Author(s):
Schmidt, M., Rohou, A., Lasker, K., Yadav, J.K., Schiene-Fischer, C., Fandrich, M., Grigorie, N.
Reference:
Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11858-63.
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Protein Information
Protein Name:
Amyloid-beta A4 protein
Alternative Name:
ABPP, APPI, Alzheimer disease amyloid protein, Amyloid precursor protein, Amyloid-beta precursor protein, Cerebral vascular amyloid peptide, PreA4, Protease nexin-II
Gene Name:
APP, A4, AD1
Sequence Length:
28
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P05067
Keyword(s):
AMYLOID BETA A4 PROTEIN
Structure Information
PDB ID:
5AEF
Amyloid Category:
Amyloid
Type:
Fibril
Global Stoichiometry:
Homo 2-mer - A2
PDB Classification:
PROTEIN FIBRIL
Method:
ELECTRON MICROSCOPY
Resolution (
Å
):
5.0
R free:
Entry:S-0413
PDB ID: 5AKS
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Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Transthyretin binding heterogeneity and anti-amyloidogenic activity of natural polyphenols and their metabolites: resveratrol-3-O- glucuronide
A main finding of this investigation was the highly preferential binding of resveratrol and thyroxine, both characterized by negative binding cooperativity, to distinct sites in TTR, consistent with the data of x-ray analysis of TTR in complex with both ligands. Although revealing the ability of the two thyroxine binding sites of TTR to discriminate between different ligands, this feature has allowed us to evaluate the interactions of polyphenols with both resveratrol and thyroxine preferential binding sites. Among flavonoids, genistein and apigenin were able to effectively displace resveratrol from its preferential binding site, whereas genistein also showed the ability to interact, albeit weakly, with the preferential thyroxine binding site. Several glucuronidated polyphenol metabolites did not exhibit significant competition for resveratrol and thyroxine preferential binding sites and lacked the ability to stabilize TTR. However, resveratrol-3-O-sulfate was able to significantly protect the protein native state.
Literature
PMID:
26468275
Author(s):
Florio, P., Folli, C., Cianci, M., Del Rio, D., Zanotti, G., Berni, R.
Reference:
J Biol Chem. 2015 Dec 11;290(50):29769-80.
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Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
TRANSTHYRETIN
Structure Information
PDB ID:
5AKS
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.25
R free:
0.188
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
R3X
A
C20 H20 O9
404.37
Resveratrol-3-O-glucuronide
c1cc(ccc1/C=C/c2cc(cc(c2)O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)C(=O)O)O)O)O)O)O
QWSAYEBSTMCFKY-OTPOQTMVSA-N
SO4
A
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
DMS
B
C2 H6 O S
78.13
DIMETHYL SULFOXIDE
CS(=O)C
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
R3X
B
C20 H20 O9
404.37
Resveratrol-3-O-glucuronide
c1cc(ccc1/C=C/c2cc(cc(c2)O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)C(=O)O)O)O)O)O)O
QWSAYEBSTMCFKY-OTPOQTMVSA-N
SO4
B
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
Entry:S-0414
PDB ID: 5AKT
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Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Transthyretin binding heterogeneity and anti-amyloidogenic activity of natural polyphenols and their metabolites: resveratrol-4'-O- glucuronide
A main finding of this investigation was the highly preferential binding of resveratrol and thyroxine, both characterized by negative binding cooperativity, to distinct sites in TTR, consistent with the data of x-ray analysis of TTR in complex with both ligands. Although revealing the ability of the two thyroxine binding sites of TTR to discriminate between different ligands, this feature has allowed us to evaluate the interactions of polyphenols with both resveratrol and thyroxine preferential binding sites. Among flavonoids, genistein and apigenin were able to effectively displace resveratrol from its preferential binding site, whereas genistein also showed the ability to interact, albeit weakly, with the preferential thyroxine binding site. Several glucuronidated polyphenol metabolites did not exhibit significant competition for resveratrol and thyroxine preferential binding sites and lacked the ability to stabilize TTR. However, resveratrol-3-O-sulfate was able to significantly protect the protein native state.
Literature
PMID:
26468275
Author(s):
Florio, P., Folli, C., Cianci, M., Del Rio, D., Zanotti, G., Berni, R.
Reference:
J Biol Chem. 2015 Dec 11;290(50):29769-80.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
TRANSTHYRETIN
Structure Information
PDB ID:
5AKT
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.35
R free:
0.195
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
R4G
A
C20 H20 O9
404.37
Resveratrol-4'-O-glucuronide
c1cc(ccc1/C=C/c2cc(cc(c2)O)O)O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)C(=O)O)O)O)O
CDEBVTGYVFHDMA-OTPOQTMVSA-N
SO4
A
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
R4G
B
C20 H20 O9
404.37
Resveratrol-4'-O-glucuronide
c1cc(ccc1/C=C/c2cc(cc(c2)O)O)O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)C(=O)O)O)O)O
CDEBVTGYVFHDMA-OTPOQTMVSA-N
Entry:S-0415
PDB ID: 5AKV
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Transthyretin binding heterogeneity and anti-amyloidogenic activity of natural polyphenols and their metabolites: genistein-7-O- glucuronide
A main finding of this investigation was the highly preferential binding of resveratrol and thyroxine, both characterized by negative binding cooperativity, to distinct sites in TTR, consistent with the data of x-ray analysis of TTR in complex with both ligands. Although revealing the ability of the two thyroxine binding sites of TTR to discriminate between different ligands, this feature has allowed us to evaluate the interactions of polyphenols with both resveratrol and thyroxine preferential binding sites. Among flavonoids, genistein and apigenin were able to effectively displace resveratrol from its preferential binding site, whereas genistein also showed the ability to interact, albeit weakly, with the preferential thyroxine binding site. Several glucuronidated polyphenol metabolites did not exhibit significant competition for resveratrol and thyroxine preferential binding sites and lacked the ability to stabilize TTR. However, resveratrol-3-O-sulfate was able to significantly protect the protein native state.
Literature
PMID:
26468275
Author(s):
Florio, P., Folli, C., Cianci, M., Del Rio, D., Zanotti, G., Berni, R.
Reference:
J Biol Chem. 2015 Dec 11;290(50):29769-80.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
TRANSTHYRETIN
Structure Information
PDB ID:
5AKV
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.52
R free:
0.2
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
G7G
A
C21 H18 O11
446.36
Genistein-7-O-glucuronide
c1cc(ccc1C2=COc3cc(cc(c3C2=O)O)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)C(=O)O)O)O)O)O
JIVINIISUDEORF-ZFORQUDYSA-N
G7G
B
C21 H18 O11
446.36
Genistein-7-O-glucuronide
c1cc(ccc1C2=COc3cc(cc(c3C2=O)O)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)C(=O)O)O)O)O)O
JIVINIISUDEORF-ZFORQUDYSA-N
Entry:S-0416
PDB ID: 5AL0
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
Description
Transthyretin binding heterogeneity and anti-amyloidogenic activity of natural polyphenols and their metabolites: resveratrol-3-O-sulfate
A main finding of this investigation was the highly preferential binding of resveratrol and thyroxine, both characterized by negative binding cooperativity, to distinct sites in TTR, consistent with the data of x-ray analysis of TTR in complex with both ligands. Although revealing the ability of the two thyroxine binding sites of TTR to discriminate between different ligands, this feature has allowed us to evaluate the interactions of polyphenols with both resveratrol and thyroxine preferential binding sites. Among flavonoids, genistein and apigenin were able to effectively displace resveratrol from its preferential binding site, whereas genistein also showed the ability to interact, albeit weakly, with the preferential thyroxine binding site. Several glucuronidated polyphenol metabolites did not exhibit significant competition for resveratrol and thyroxine preferential binding sites and lacked the ability to stabilize TTR. However, resveratrol-3-O-sulfate was able to significantly protect the protein native state.
Literature
PMID:
26468275
Author(s):
Florio, P., Folli, C., Cianci, M., Del Rio, D., Zanotti, G., Berni, R.
Reference:
J Biol Chem. 2015 Dec 11;290(50):29769-80.
Download
Entry:
CSV
JSON
Structure:
PDB
CIF
FASTA
Contact Network:
CSV
JSON
Protein Information
Protein Name:
Transthyretin
Alternative Name:
ATTR, Prealbumin, TBPA
Gene Name:
TTR, PALB
Sequence Length:
127
Species:
Homo sapiens
Mutation(s):
No
E.C. Number:
UniProt ID:
P02766
Keyword(s):
TRANSTHYRETIN
Structure Information
PDB ID:
5AL0
Amyloid Category:
Non-amyloid
Type:
Inhibitor complex
Global Stoichiometry:
Homo 4-mer - A4
PDB Classification:
TRANSPORT PROTEIN
Method:
X-RAY DIFFRACTION
Resolution (
Å
):
1.39
R free:
0.209
Ligand Information
Ligand ID
Chain ID
Ligand Formula
Ligand MW
Ligand Name
Ligand SMILES
InChI Key
DMS
A
C2 H6 O S
78.13
DIMETHYL SULFOXIDE
CS(=O)C
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
R3S
A
C14 H12 O6 S
308.31
RESVERATROL-3-O-SULFATE
c1cc(ccc1/C=C/c2cc(cc(c2)OS(=O)(=O)O)O)O
DULQFFCIVGYOFH-OWOJBTEDSA-N
SO4
A
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
R3S
B
C14 H12 O6 S
308.31
RESVERATROL-3-O-SULFATE
c1cc(ccc1/C=C/c2cc(cc(c2)OS(=O)(=O)O)O)O
DULQFFCIVGYOFH-OWOJBTEDSA-N
SO4
B
O4 S -2
96.06
SULFATE ION
[O-]S(=O)(=O)[O-]
QAOWNCQODCNURD-UHFFFAOYSA-L
Entry:S-0417
PDB ID: 5AL8
CSV
JSON
Close ×
Structure
Press 'p' to pause
View interactive contact network
Protein Contacts Atlas
Sequence & Sec. Str.
Chain 1
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Chain 2
1
G
P
T
G
T
G
E
S
K
C
P
L
M
V
K
V
L
D
A
V
R
G
S
P
A
25
26
I
N
V
A
V
H
V
F
R
K
A
A
D
D
T
W
E
P
F
A
S
G
K
T
S
50
51
E
S
G
E
L
H
G
L
T
T
E
E
E
F
V
E
G
I
Y
K
V
E
I
D
T
75
76
K
S
Y
W
K
A
L
G
I
S
P
F
H
E
H
A
E
V
V
F
T
A
N
D
S
100
101
G
P
R
R
Y
T
I
A
A
L
L
S
P
Y
S
Y
S
T
T
A
V
V
T
N
P
125
126
K
E
127
Helix: Magenta; Strand: Yellow; Coil & Turn: White.
Charged residues and Proline are highlighed in blue.
