CPAD 2.0

Entry	PDB ID	Protein Name	Species	Length	Mutation(s)	Class	Type	Method	Resolution (Å)	PMID
S-0181	2Y3K	Amyloid-beta A4 protein	Homo sapiens	8	No	Amyloid	Fibril	X-RAY DIFFRACTION	1.9	21949245
S-0182	2Y3L	Amyloid-beta A4 protein	Homo sapiens	8	No	Amyloid	Fibril	X-RAY DIFFRACTION	2.1	21949245
S-0183	2Z9T	Beta-2-microglobulin	Homo sapiens	100	W60G	Non-amyloid	Protein	X-RAY DIFFRACTION	1.8	18395224
S-0184	3A4D	Transthyretin	Homo sapiens	127	No	Amyloid	Protein	X-RAY DIFFRACTION	2.0	19950966
S-0185	3A4E	Transthyretin	Homo sapiens	127	E54G	Amyloid	Protein	X-RAY DIFFRACTION	1.7	19950966
S-0186	3A4F	Transthyretin	Homo sapiens	127	E54K	Amyloid	Protein	X-RAY DIFFRACTION	1.99	19950966
S-0187	3B56	Transthyretin	Homo sapiens	127	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.55	18155178
S-0188	3B5G	Immunoglobin lambda 6 light-chain	Homo sapiens	111	P7S	Amyloid	Protein	X-RAY DIFFRACTION	1.9	19941869
S-0189	3BAE	Amyloid-beta A4 protein		28 , 228 , 218	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.59	18237744
S-0190	3BDX	Amyloid lambda 6 light chain variable region PIP	Homo sapiens	111	P7S	Amyloid	Protein	X-RAY DIFFRACTION	2.3	19941869
S-0191	3BKJ	Amyloid-beta A4 protein		16 , 224 , 252	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.59	18237744
S-0192	3CAE	Endonuclease I	Escherichia virus T7	132	No	Amyloid	Aggregating complex	X-RAY DIFFRACTION	3.0	18552127
S-0193	3CBR	Transthyretin	Homo sapiens	127	No	Amyloid	Protein	X-RAY DIFFRACTION	1.7	18662699
S-0194	3CDC	Immunoglobulin kappa variable 1-33	Homo sapiens	109	N34I/Y87H	Amyloid	Protein	X-RAY DIFFRACTION	1.53	18768467
S-0195	3CDF	Immunoglobulin kappa variable 1-33	Homo sapiens	109	Y87H	Amyloid	Protein	X-RAY DIFFRACTION	1.53	18768467
S-0196	3CFM	Transthyretin	Homo sapiens	118	No	Amyloid	Protein	X-RAY DIFFRACTION	1.6	19954984
S-0197	3CFN	Transthyretin	Homo sapiens	118	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.87	19954984
S-0198	3CFQ	Transthyretin	Homo sapiens	118	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	2.09	19954984
S-0199	3CFT	Transthyretin	Homo sapiens	118	No	Amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.87	19954984
S-0200	3CIQ	Beta-2-microglobulin	Homo sapiens	100	No	Amyloid	Aggregating complex	X-RAY DIFFRACTION	2.9	19172750
S-0201	3CN0	Transthyretin	Homo sapiens	127	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.52	18811132
S-0202	3CN1	Transthyretin	Homo sapiens	127	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.52	18811132
S-0203	3CN2	Transthyretin	Homo sapiens	127	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.52	18811132
S-0204	3CN3	Transthyretin	Homo sapiens	127	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.8	18811132
S-0205	3CN4	Transthyretin	Homo sapiens	127	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.4	18811132
S-0206	3D2T	Transthyretin	Homo sapiens	127	No	Non-amyloid	Inhibitor complex	X-RAY DIFFRACTION	1.85	14711308
S-0207	3D7P	Transthyretin	Homo sapiens	127	No	Amyloid	Protein	X-RAY DIFFRACTION	1.72	18662699
S-0208	3DG1	Islet amyloid polypeptide	Homo sapiens	6	No	Amyloid	Fibril	X-RAY DIFFRACTION	1.66	18556473
S-0209	3DGD	Transthyretin	Homo sapiens	127	F87M/L110M	Amyloid	Aggregating complex	X-RAY DIFFRACTION	1.383	20659897
S-0210	3DGJ	Amylin		7	No	Amyloid	Fibril	X-RAY DIFFRACTION	1.8	18556473

Structure

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View interactive contact network
Protein Contacts Atlas

Sequence & Sec. Str.

Chain 1

1

M

V

G

V

I

A

8

Chain 2

1

M

V

G

V

I

A

8

Chain 3

1

M

V

G

V

I

A

8

Chain 4

1

M

V

G

V

I

A

8

Chain 5

1

M

V

G

V

I

A

8

Chain 6

1

M

V

G

V

I

A

8

Chain 7

1

M

V

G

V

I

A

8

Chain 8

1

M

V

G

V

I

A

8

Helix: Magenta; Strand: Yellow; Coil & Turn: White.

Charged residues and Proline are highlighed in blue.

Description

Structure of segment MVGGVVIA from the amyloid-beta peptide (Ab, residues 35-42), alternate polymorph 1

ABeta molecules form Beta-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of ABeta has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. They determined eight new microcrystal structures of fiber-forming segments of ABeta. These structures, all of short, self-complementing pairs of Beta-sheets termed steric zippers, reveal a variety of modes of self-association of ABeta.

Literature

PMID:	21949245
Author(s):	Colletier, J., Laganowsky, A., Landau, M., Zhao, M., Soriaga, A.B., Goldschmidt, L., Flot, D., Cascio, D., Sawaya, M.R., Eisenberg, D.
Reference:	Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):16938-43.

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Entry:	CSV JSON
Structure:	PDB CIF FASTA
Contact Network:	CSV JSON

Protein Information

Protein Name:	Amyloid-beta A4 protein
Alternative Name:
Gene Name:
Sequence Length:	8
Species:	Homo sapiens
Mutation(s):	No
E.C. Number:
UniProt ID:	P05067
Keyword(s):	AMYLOID BETA A4 PROTEIN

Structure Information

PDB ID:	2Y3K
Amyloid Category:	Amyloid
Type:	Fibril
Global Stoichiometry:	Homo 2-mer - A2
PDB Classification:	PROTEIN FIBRIL
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.9
R free:	0.231

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

Crystal structure of Human Transthyretin (wild-type)

Crystal structure of wild-type Human Transthyretin. They have analyzed the crystal structures and biochemical and biophysical properties of E54G and E54K TTRs. The direction of the Lys15 side chain in E54K TTR and the surface electrostatic potential in the edge region in both variants were different from those of wild-type TTR. The presence of Lys54 leads to destabilization of tetramer structure due to enhanced electrostatic repulsion between Lys15 of two monomers. Consistent with structural data, the biochemical analyses demonstrated that E54G and E54K TTRs were more unstable than wild-type TTR. Furthermore, the entrance of the thyroxine (T(4)) binding pocket in TTR was markedly narrower in E54K TTR and wider in E54G TTR compared with wild-type TTR. The tetramer stabilization and amyloid fibril formation assays in the presence of T(4) showed lower tetramer stability and more fibril formation in E54K and E54G TTRs than in wild-type TTR, suggesting decreased T(4) binding to the TTR variants. These findings indicate that structural modification by Glu54 point mutation may sufficiently alter tetramer stability and T(4) binding.

Literature

PMID:	19950966
Author(s):	Miyata, M., Sato, T., Mizuguchi, M., Nakamura, T., Ikemizu, S., Nabeshima, Y., Susuki, S., Suwa, Y., Morioka, H., Ando, Y., Suico, M.A., Shuto, T., Koga, T., Yamagata, Y., Kai, H.
Reference:	Biochemistry. 2010 Jan 12;49(1):114-23.

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:	3A4D
Amyloid Category:	Amyloid
Type:	Protein
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	TRANSPORT PROTEIN
Method:	X-RAY DIFFRACTION
Resolution (Å):	2.0
R free:	0.22899999

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
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

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

Crystal structure of Human Transthyretin (E54G)

Crystal structure of Human Transthyretin with E54G mutation. They have analyzed the crystal structures and biochemical and biophysical properties of E54G and E54K TTRs. The direction of the Lys15 side chain in E54K TTR and the surface electrostatic potential in the edge region in both variants were different from those of wild-type TTR. The presence of Lys54 leads to destabilization of tetramer structure due to enhanced electrostatic repulsion between Lys15 of two monomers. Consistent with structural data, the biochemical analyses demonstrated that E54G and E54K TTRs were more unstable than wild-type TTR. Furthermore, the entrance of the thyroxine (T(4)) binding pocket in TTR was markedly narrower in E54K TTR and wider in E54G TTR compared with wild-type TTR. The tetramer stabilization and amyloid fibril formation assays in the presence of T(4) showed lower tetramer stability and more fibril formation in E54K and E54G TTRs than in wild-type TTR, suggesting decreased T(4) binding to the TTR variants. These findings indicate that structural modification by Glu54 point mutation may sufficiently alter tetramer stability and T(4) binding.

Literature

PMID:	19950966
Author(s):	Miyata, M., Sato, T., Mizuguchi, M., Nakamura, T., Ikemizu, S., Nabeshima, Y., Susuki, S., Suwa, Y., Morioka, H., Ando, Y., Suico, M.A., Shuto, T., Koga, T., Yamagata, Y., Kai, H.
Reference:	Biochemistry. 2010 Jan 12;49(1):114-23.

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):	E54G
E.C. Number:
UniProt ID:	P02766
Keyword(s):	Transthyretin

Structure Information

PDB ID:	3A4E
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:	0.23800000

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
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

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

K

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

K

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

Crystal Structure of Human Transthyretin (E54K)

Crystal structure of Human Transthyretin with E54K mutation. They have analyzed the crystal structures and biochemical and biophysical properties of E54G and E54K TTRs. The direction of the Lys15 side chain in E54K TTR and the surface electrostatic potential in the edge region in both variants were different from those of wild-type TTR. The presence of Lys54 leads to destabilization of tetramer structure due to enhanced electrostatic repulsion between Lys15 of two monomers. Consistent with structural data, the biochemical analyses demonstrated that E54G and E54K TTRs were more unstable than wild-type TTR. Furthermore, the entrance of the thyroxine (T(4)) binding pocket in TTR was markedly narrower in E54K TTR and wider in E54G TTR compared with wild-type TTR. The tetramer stabilization and amyloid fibril formation assays in the presence of T(4) showed lower tetramer stability and more fibril formation in E54K and E54G TTRs than in wild-type TTR, suggesting decreased T(4) binding to the TTR variants. These findings indicate that structural modification by Glu54 point mutation may sufficiently alter tetramer stability and T(4) binding.

Literature

PMID:	19950966
Author(s):	Miyata, M., Sato, T., Mizuguchi, M., Nakamura, T., Ikemizu, S., Nabeshima, Y., Susuki, S., Suwa, Y., Morioka, H., Ando, Y., Suico, M.A., Shuto, T., Koga, T., Yamagata, Y., Kai, H.
Reference:	Biochemistry. 2010 Jan 12;49(1):114-23.

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):	E54K
E.C. Number:
UniProt ID:	P02766
Keyword(s):	Transthyretin

Structure Information

PDB ID:	3A4F
Amyloid Category:	Amyloid
Type:	Protein
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	TRANSPORT PROTEIN
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.99
R free:	0.223

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
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

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

Crystal structure of transthyretin in complex with 3,5-diiodosalicylic acid

A number of structurally diverse small molecules that bind to the TTR channel increasing the protein stability and thereafter inhibiting amyloid fibrillogenesis have been tested. In order to take advantage of the high propensity to interactions between iodine substituents and the TTR channel. they have identified iodinated derivative of salicylic acid 3,5-diiodosalicylic acid, available commercially. The paper reports relative binding affinities of salicylic acid and the iodinated derivative and the crystal structure of TTR complexed with 3,5-diiodosalicylic acid, to elucidate the higher binding affinity of this compound towards TTR.

Literature

PMID:	18155178
Author(s):	Gales, L., Almeida, M.R., Arsequell, G., Valencia, G., Saraiva, M.J., Damas, A.M.
Reference:	Biochim Biophys Acta. 2008 Mar;1784(3):512-7. Epub 2007 Dec 3

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:	3B56
Amyloid Category:	Non-amyloid
Type:	Inhibitor complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	TRANSPORT PROTEIN
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.55
R free:	0.214

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
DIU	A	C7 H4 I2 O3	389.91	2-HYDROXY-3,5-DIIODO-BENZOIC ACID	c1c(cc(c(c1C(=O)O)O)I)I	DHZVWQPHNWDCFS-UHFFFAOYSA-N
DIU	B	C7 H4 I2 O3	389.91	2-HYDROXY-3,5-DIIODO-BENZOIC ACID	c1c(cc(c(c1C(=O)O)O)I)I	DHZVWQPHNWDCFS-UHFFFAOYSA-N

Structure

Press 'p' to pause
View interactive contact network
Protein Contacts Atlas

Sequence & Sec. Str.

Chain 1

1

N

F

M

L

T

Q

S

H

S

V

S

E

S

P

G

K

T

V

T

I

S

C

T

R

S

25

26

S

G

S

I

A

S

N

Y

V

Q

W

Y

Q

R

P

G

S

P

T

V

I

Y

50

51

E

D

N

Q

R

P

S

G

V

P

D

R

F

S

G

S

I

D

S

N

S

A

S

75

76

L

T

I

S

G

L

K

T

E

D

E

A

D

Y

C

Q

S

Y

D

S

N

H

V

100

101

V

F

G

T

K

L

T

V

L

111

Chain 2

1

N

F

M

L

T

Q

S

H

S

V

S

E

S

P

G

K

T

V

T

I

S

C

T

R

S

25

26

S

G

S

I

A

S

N

Y

V

Q

W

Y

Q

R

P

G

S

P

T

V

I

Y

50

51

E

D

N

Q

R

P

S

G

V

P

D

R

F

S

G

S

I

D

S

N

S

A

S

75

76

L

T

I

S

G

L

K

T

E

D

E

A

D

Y

C

Q

S

Y

D

S

N

H

V

100

101

V

F

G

T

K

L

T

V

L

111

Helix: Magenta; Strand: Yellow; Coil & Turn: White.

Charged residues and Proline are highlighed in blue.

Description

Crystal Structure of the Unstable and Highly Fibrillogenic PRO7SER Mutant of the Recombinant Variable Domain 6AJL2

They report the thermodynamic and in vitro fibrillogenic properties of several mutants of the lambda6 protein 6aJL2 in which Pro7 and/or His8 was substituted by Ser or Pro. The H8P and H8S mutants were almost as stable as the wild-type protein and were poorly fibrillogenic. In contrast, the P7S mutation decreased the thermodynamic stability of 6aJL2 and greatly enhanced its capacity to form amyloid-like fibrils in vitro. The crystal structure of the P7S mutant showed that the substitution induced both local and long-distance effects, such as the rearrangement of the V(L) (variable region of the light chain)-V(L) interface. in Space Group: P 2(1) 2(1) 2(1)

Literature

PMID:	19941869
Author(s):	Hernandez-Santoyo, A., del Pozo Yauner, L., Fuentes-Silva, D., Ortiz, E., Rudino-Pinera, E., Sanchez-Lopez, R., Horjales, E., Becerril, B., Rodriguez-Romero, A.
Reference:	J Mol Biol. 2010 Feb 19;396(2):280-92.

Download

Entry:	CSV JSON
Structure:	PDB CIF FASTA
Contact Network:	CSV JSON

Protein Information

Protein Name:	Immunoglobin lambda 6 light-chain
Alternative Name:
Gene Name:
Sequence Length:	111
Species:	Homo sapiens
Mutation(s):	P7S
E.C. Number:
UniProt ID:
Keyword(s):	AMYLOID LAMBDA 6 LIGHT CHAIN VARIABLE REGION PIP

Structure Information

PDB ID:	3B5G
Amyloid Category:	Amyloid
Type:	Protein
Global Stoichiometry:	Homo 2-mer - A2
PDB Classification:	IMMUNE SYSTEM
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.9
R free:	0.21

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
ACT	A	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
GOL	A	C3 H8 O3	92.09	GLYCEROL	C(C(CO)O)O	PEDCQBHIVMGVHV-UHFFFAOYSA-N
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

Structure

Press 'p' to pause
View interactive contact network
Protein Contacts Atlas

Sequence & Sec. Str.

Chain 1

1

N

F

M

L

T

Q

S

H

S

V

S

E

S

P

G

K

T

V

T

I

S

C

T

R

S

25

26

S

G

S

I

A

S

N

Y

V

Q

W

Y

Q

R

P

G

S

P

T

V

I

Y

50

51

E

D

N

Q

R

P

S

G

V

P

D

R

F

S

G

S

I

D

S

N

S

A

S

75

76

L

T

I

S

G

L

K

T

E

D

E

A

D

Y

C

Q

S

Y

D

S

N

H

V

100

101

V

F

G

T

K

L

T

V

L

111

Chain 2

1

N

F

M

L

T

Q

S

H

S

V

S

E

S

P

G

K

T

V

T

I

S

C

T

R

S

25

26

S

G

S

I

A

S

N

Y

V

Q

W

Y

Q

R

P

G

S

P

T

V

I

Y

50

51

E

D

N

Q

R

P

S

G

V

P

D

R

F

S

G

S

I

D

S

N

S

A

S

75

76

L

T

I

S

G

L

K

T

E

D

E

A

D

Y

C

Q

S

Y

D

S

N

H

V

100

101

V

F

G

T

K

L

T

V

L

111

Chain 3

1

N

F

M

L

T

Q

S

H

S

V

S

E

S

P

G

K

T

V

T

I

S

C

T

R

S

25

26

S

G

S

I

A

S

N

Y

V

Q

W

Y

Q

R

P

G

S

P

T

V

I

Y

50

51

E

D

N

Q

R

P

S

G

V

P

D

R

F

S

G

S

I

D

S

N

S

A

S

75

76

L

T

I

S

G

L

K

T

E

D

E

A

D

Y

C

Q

S

Y

D

S

N

H

V

100

101

V

F

G

T

K

L

T

V

L

111

Helix: Magenta; Strand: Yellow; Coil & Turn: White.

Charged residues and Proline are highlighed in blue.

Description

Crystal Structure of the Unstable and Highly Fibrillogenic PRO7SER Mutant of the Recombinant Variable Domain 6AJL2

They report the thermodynamic and in vitro fibrillogenic properties of several mutants of the lambda6 protein 6aJL2 in which Pro7 and/or His8 was substituted by Ser or Pro. The H8P and H8S mutants were almost as stable as the wild-type protein and were poorly fibrillogenic. In contrast, the P7S mutation decreased the thermodynamic stability of 6aJL2 and greatly enhanced its capacity to form amyloid-like fibrils in vitro. The crystal structure of the P7S mutant showed that the substitution induced both local and long-distance effects, such as the rearrangement of the V(L) (variable region of the light chain)-V(L) interface. in Space Group: C 2 2 2(1)

Literature

PMID:	19941869
Author(s):	Hernandez-Santoyo, A., del Pozo Yauner, L., Fuentes-Silva, D., Ortiz, E., Rudino-Pinera, E., Sanchez-Lopez, R., Horjales, E., Becerril, B., Rodriguez-Romero, A.
Reference:	J Mol Biol. 2010 Feb 19;396(2):280-92.

Download

Entry:	CSV JSON
Structure:	PDB CIF FASTA
Contact Network:	CSV JSON

Protein Information

Protein Name:	Amyloid lambda 6 light chain variable region PIP
Alternative Name:
Gene Name:
Sequence Length:	111
Species:	Homo sapiens
Mutation(s):	P7S
E.C. Number:
UniProt ID:	Q96JD1
Keyword(s):	Amyloid lambda 6 light chain variable region PIP (fragment)

Structure Information

PDB ID:	3BDX
Amyloid Category:	Amyloid
Type:	Protein
Global Stoichiometry:	Homo 2-mer - A2
PDB Classification:	IMMUNE SYSTEM
Method:	X-RAY DIFFRACTION
Resolution (Å):	2.3
R free:	0.24600000

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
ACT	A	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
GOL	A	C3 H8 O3	92.09	GLYCEROL	C(C(CO)O)O	PEDCQBHIVMGVHV-UHFFFAOYSA-N
ACT	B	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
GOL	B	C3 H8 O3	92.09	GLYCEROL	C(C(CO)O)O	PEDCQBHIVMGVHV-UHFFFAOYSA-N
MES	B	C6 H13 N O4 S	195.24	2-(N-MORPHOLINO)-ETHANESULFONIC ACID	C1COCC[NH+]1CCS(=O)(=O)[O-]	SXGZJKUKBWWHRA-UHFFFAOYSA-N
ACT	C	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
GOL	C	C3 H8 O3	92.09	GLYCEROL	C(C(CO)O)O	PEDCQBHIVMGVHV-UHFFFAOYSA-N

Structure

Press 'p' to pause
View interactive contact network
Protein Contacts Atlas

Sequence & Sec. Str.

Chain 1

1

C

P

L

M

V

K

V

L

D

A

V

R

G

S

P

A

I

N

V

A

V

H

V

F

R

25

26

K

A

D

T

W

E

P

F

A

S

G

K

T

S

E

S

G

E

L

H

G

L

T

50

51

T

E

F

V

E

G

I

Y

K

V

E

I

D

T

K

S

Y

W

K

A

L

G

I

75

76

S

P

F

H

E

H

A

E

V

F

T

A

N

D

S

G

P

R

Y

T

I

A

100

101

L

S

P

Y

S

Y

S

T

A

V

T

N

P

K

E

118

Chain 2

1

C

P

L

M

V

K

V

L

D

A

V

R

G

S

P

A

I

N

V

A

V

H

V

F

R

25

26

K

A

D

T

W

E

P

F

A

S

G

K

T

S

E

S

G

E

L

H

G

L

T

50

51

T

E

F

V

E

G

I

Y

K

V

E

I

D

T

K

S

Y

W

K

A

L

G

I

75

76

S

P

F

H

E

H

A

E

V

F

T

A

N

D

S

G

P

R

Y

T

I

A

100

101

L

S

P

Y

S

Y

S

T

A

V

T

N

P

K

E

118

Helix: Magenta; Strand: Yellow; Coil & Turn: White.

Charged residues and Proline are highlighed in blue.

Description

Crystal structure of human transthyretin in complex with 1-anilino-8-naphthalene sulfonate ( 44% wtTTR fibril formation inhibition)

Structural analysis of the interactions of TTR with 1-anilino-8-naphthalene sulfonate (1,8-ANS). Crystal structure of TTR:1,8-ANS complex reveals a peculiar interaction, through the stacking of the naphthalene ring between the side-chain of Lys15 and Leu17. The sulfonate moiety provides additional interaction with Lys15' and a water-mediated hydrogen bond with Thr119'. 1,8-ANS inhibits the fibril formation.

Literature

PMID:	19954984
Author(s):	Lima, L.M., Silva, V.D., Palmieri, L.D., Oliveira, M.C., Foguel, D., Polikarpov, I.
Reference:	Bioorg Med Chem. 2010 Jan 1;18(1):100-10.

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:	118
Species:	Homo sapiens
Mutation(s):	No
E.C. Number:
UniProt ID:	P02766
Keyword(s):	Transthyretin

Structure Information

PDB ID:	3CFN
Amyloid Category:	Non-amyloid
Type:	Inhibitor complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	TRANSPORT PROTEIN
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.87
R free:	0.245

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
2AN	A	C16 H13 N O3 S	299.34	8-ANILINO-1-NAPHTHALENE SULFONATE	c1ccc(cc1)Nc2cccc3c2c(ccc3)S(=O)(=O)O	FWEOQOXTVHGIFQ-UHFFFAOYSA-N
2AN	B	C16 H13 N O3 S	299.34	8-ANILINO-1-NAPHTHALENE SULFONATE	c1ccc(cc1)Nc2cccc3c2c(ccc3)S(=O)(=O)O	FWEOQOXTVHGIFQ-UHFFFAOYSA-N

Structure

Press 'p' to pause
View interactive contact network
Protein Contacts Atlas

Sequence & Sec. Str.

Chain 1

1

C

P

L

M

V

K

V

L

D

A

V

R

G

S

P

A

I

N

V

A

V

H

V

F

R

25

26

K

A

D

T

W

E

P

F

A

S

G

K

T

S

E

S

G

E

L

H

G

L

T

50

51

T

E

F

V

E

G

I

Y

K

V

E

I

D

T

K

S

Y

W

K

A

L

G

I

75

76

S

P

F

H

E

H

A

E

V

F

T

A

N

D

S

G

P

R

Y

T

I

A

100

101

L

S

P

Y

S

Y

S

T

A

V

T

N

P

K

E

118

Chain 2

1

C

P

L

M

V

K

V

L

D

A

V

R

G

S

P

A

I

N

V

A

V

H

V

F

R

25

26

K

A

D

T

W

E

P

F

A

S

G

K

T

S

E

S

G

E

L

H

G

L

T

50

51

T

E

F

V

E

G

I

Y

K

V

E

I

D

T

K

S

Y

W

K

A

L

G

I

75

76

S

P

F

H

E

H

A

E

V

F

T

A

N

D

S

G

P

R

Y

T

I

A

100

101

L

S

P

Y

S

Y

S

T

A

V

T

N

P

K

E

118

Helix: Magenta; Strand: Yellow; Coil & Turn: White.

Charged residues and Proline are highlighed in blue.

Description

Crystal structure of human wild-type transthyretin in complex with diclofenac (33% wtTTR fibril formation inhibition)

Crystal structure of human wild-type transthyretin in complex with diclofenac, a ligand that inhibits the fibril formation.

Literature

PMID:	19954984
Author(s):	Lima, L.M., Silva, V.D., Palmieri, L.D., Oliveira, M.C., Foguel, D., Polikarpov, I.
Reference:	Bioorg Med Chem. 2010 Jan 1;18(1):100-10.

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:	118
Species:	Homo sapiens
Mutation(s):	No
E.C. Number:
UniProt ID:	P02766
Keyword(s):	Transthyretin

Structure Information

PDB ID:	3CFQ
Amyloid Category:	Non-amyloid
Type:	Inhibitor complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	TRANSPORT PROTEIN
Method:	X-RAY DIFFRACTION
Resolution (Å):	2.09
R free:	0.249

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
DIF	A	C14 H11 Cl2 N O2	296.15	2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID	c1ccc(c(c1)CC(=O)O)Nc2c(cccc2Cl)Cl	DCOPUUMXTXDBNB-UHFFFAOYSA-N
DIF	B	C14 H11 Cl2 N O2	296.15	2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID	c1ccc(c(c1)CC(=O)O)Nc2c(cccc2Cl)Cl	DCOPUUMXTXDBNB-UHFFFAOYSA-N

Structure

Press 'p' to pause
View interactive contact network
Protein Contacts Atlas

Sequence & Sec. Str.

Chain 1

1

C

P

L

M

V

K

V

L

D

A

V

R

G

S

P

A

I

N

V

A

V

H

V

F

R

25

26

K

A

D

T

W

E

P

F

A

S

G

K

T

S

E

S

G

E

L

H

G

L

T

50

51

T

E

F

V

E

G

I

Y

K

V

E

I

D

T

K

S

Y

W

K

A

L

G

I

75

76

S

P

F

H

E

H

A

E

V

F

T

A

N

D

S

G

P

R

Y

T

I

A

100

101

L

S

P

Y

S

Y

S

T

A

V

T

N

P

K

E

118

Chain 2

1

C

P

L

M

V

K

V

L

D

A

V

R

G

S

P

A

I

N

V

A

V

H

V

F

R

25

26

K

A

D

T

W

E

P

F

A

S

G

K

T

S

E

S

G

E

L

H

G

L

T

50

51

T

E

F

V

E

G

I

Y

K

V

E

I

D

T

K

S

Y

W

K

A

L

G

I

75

76

S

P

F

H

E

H

A

E

V

F

T

A

N

D

S

G

P

R

Y

T

I

A

100

101

L

S

P

Y

S

Y

S

T

A

V

T

N

P

K

E

118

Helix: Magenta; Strand: Yellow; Coil & Turn: White.

Charged residues and Proline are highlighed in blue.

Description

Crystal structure of human transthyretin in complex with 1-amino-5-naphthalene sulfonate (100% wtTTR fibril formation inhibition)

The crystal structure of TTR in complex with the weak analogue 1,5-AmNS, the binding is driven mainly by hydrophobic partition and one electrostatic interaction between the sulfonate group and the Lys15. The inhibition of fibril formation was insignificant with this ligand.

Literature

PMID:	19954984
Author(s):	Lima, L.M., Silva, V.D., Palmieri, L.D., Oliveira, M.C., Foguel, D., Polikarpov, I.
Reference:	Bioorg Med Chem. 2010 Jan 1;18(1):100-10.

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:	118
Species:	Homo sapiens
Mutation(s):	No
E.C. Number:
UniProt ID:	P02766
Keyword(s):	Transthyretin

Structure Information

PDB ID:	3CFT
Amyloid Category:	Amyloid
Type:	Inhibitor complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	TRANSPORT PROTEIN
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.87
R free:	0.239

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
5NS	A	C10 H9 N O3 S	223.25	5-aminonaphthalene-1-sulfonic acid	c1cc2c(cccc2S(=O)(=O)O)c(c1)N	DQNAQOYOSRJXFZ-UHFFFAOYSA-N
5NS	B	C10 H9 N O3 S	223.25	5-aminonaphthalene-1-sulfonic acid	c1cc2c(cccc2S(=O)(=O)O)c(c1)N	DQNAQOYOSRJXFZ-UHFFFAOYSA-N

Structure

Press 'p' to pause
View interactive contact network
Protein Contacts Atlas

Sequence & Sec. Str.

Chain 1

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 2

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 3

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

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50

51

E

H

S

D

L

S

F

S

K

D

W

S

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Y

L

Y

T

E

F

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P

T

E

75

76

K

D

E

Y

A

C

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V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 4

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

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50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 5

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

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N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

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K

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50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

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F

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P

T

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75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 6

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

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D

M

100

Chain 7

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 8

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 9

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 10

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 11

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Chain 12

1

M

I

Q

R

T

P

K

I

Q

V

Y

S

R

F

P

A

E

N

G

K

S

N

F

L

N

25

26

C

Y

V

S

G

F

H

P

S

D

I

E

V

D

L

K

N

G

E

R

I

E

K

V

50

51

E

H

S

D

L

S

F

S

K

D

W

S

F

Y

L

Y

T

E

F

T

P

T

E

75

76

K

D

E

Y

A

C

R

V

N

H

V

T

L

S

Q

P

K

I

V

K

W

D

R

D

M

100

Helix: Magenta; Strand: Yellow; Coil & Turn: White.

Charged residues and Proline are highlighed in blue.

Description

A regulatable switch mediates self-association in an immunoglobulin fold

For Beta2m, oligomerization into pre-amyloidogenic states occurs in specific response to coordination by Cu2+. Metal is not a direct participant in the molecular interface. Rather, binding results in distal alterations enabling the formation of two new surfaces. These interact to form a closed hexameric species. The origins of this include isomerization of a buried and conserved cis-proline previously implicated in the Beta2m aggregation pathway.

Literature

PMID:	19172750
Author(s):	Calabrese, M.F., Eakin, C.M., Wang, J.M., Miranker, A.D.
Reference:	Nat Struct Mol Biol. 2008 Sep;15(9):965-71

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Entry:	CSV JSON
Structure:	PDB CIF FASTA
Contact Network:	CSV JSON

Protein Information

Protein Name:	Beta-2-microglobulin
Alternative Name:
Gene Name:	B2M, CDABP0092, HDCMA22P
Sequence Length:	100
Species:	Homo sapiens
Mutation(s):	No
E.C. Number:
UniProt ID:	P61769
Keyword(s):	Beta-2-microglobulin

Structure Information

PDB ID:	3CIQ
Amyloid Category:	Amyloid
Type:	Aggregating complex
Global Stoichiometry:	Homo 6-mer - A6
PDB Classification:	IMMUNE SYSTEM
Method:	X-RAY DIFFRACTION
Resolution (Å):	2.9
R free:	0.264

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
CU	A	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	B	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	C	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	D	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	E	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	F	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	G	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
TLA	G	C4 H6 O6	150.09	L(+)-TARTARIC ACID	[C@@H]([C@H](C(=O)O)O)(C(=O)O)O	FEWJPZIEWOKRBE-JCYAYHJZSA-N
CU	H	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	I	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	J	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	K	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N
CU	L	Cu 2	63.55	COPPER (II) ION	[Cu+2]	JPVYNHNXODAKFH-UHFFFAOYSA-N

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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) in complex with 3,5-Dimethyl-4-hydroxystilbene

To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. They have evaluated bisaryl molecules with linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3).

Literature

PMID:	18811132
Author(s):	Johnson, S.M., Connelly, S., Wilson, I.A., Kelly, J.W.
Reference:	J Med Chem. 2008 Oct 23;51(20):6348-58.

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:	3CN0
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:	0.18899999

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
LJ1	A	C16 H16 O	224.3	2,6-dimethyl-4-[(E)-2-phenylethenyl]phenol	Cc1cc(cc(c1O)C)C=Cc2ccccc2	PAHKYLUYTGBFNW-CMDGGOBGSA-N
LJ1	B	C16 H16 O	224.3	2,6-dimethyl-4-[(E)-2-phenylethenyl]phenol	Cc1cc(cc(c1O)C)C=Cc2ccccc2	PAHKYLUYTGBFNW-CMDGGOBGSA-N

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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) in complex with 3,5-Dibromo-4-hydroxystilbene

To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. They have evaluated bisaryl molecules with linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3).

Literature

PMID:	18811132
Author(s):	Johnson, S.M., Connelly, S., Wilson, I.A., Kelly, J.W.
Reference:	J Med Chem. 2008 Oct 23;51(20):6348-58.

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:	3CN1
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:	0.188

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
LJ2	A	C14 H10 Br2 O	354.04	2,6-dibromo-4-[(E)-2-phenylethenyl]phenol	c1ccc(cc1)C=Cc2cc(c(c(c2)Br)O)Br	WMVYUPRIADVLTH-VOTSOKGWSA-N
LJ2	B	C14 H10 Br2 O	354.04	2,6-dibromo-4-[(E)-2-phenylethenyl]phenol	c1ccc(cc1)C=Cc2cc(c(c(c2)Br)O)Br	WMVYUPRIADVLTH-VOTSOKGWSA-N

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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) in complex with 3,5-Dibromo-4-hydroxybiphenyl

To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. They have evaluated bisaryl molecules with linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3).

Literature

PMID:	18811132
Author(s):	Johnson, S.M., Connelly, S., Wilson, I.A., Kelly, J.W.
Reference:	J Med Chem. 2008 Oct 23;51(20):6348-58.

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:	3CN2
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:	0.19699999

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
LJ3	A	C12 H8 Br2 O	328.0	3,5-dibromobiphenyl-4-ol	c1ccc(cc1)c2cc(c(c(c2)Br)O)Br	SKQRVOXIIAXXEM-UHFFFAOYSA-N
LJ3	B	C12 H8 Br2 O	328.0	3,5-dibromobiphenyl-4-ol	c1ccc(cc1)c2cc(c(c(c2)Br)O)Br	SKQRVOXIIAXXEM-UHFFFAOYSA-N

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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) in complex with 1,3-Dibromo-2-hydroxy-5-phenoxybenzene

To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. They have evaluated bisaryl molecules with linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3).

Literature

PMID:	18811132
Author(s):	Johnson, S.M., Connelly, S., Wilson, I.A., Kelly, J.W.
Reference:	J Med Chem. 2008 Oct 23;51(20):6348-58.

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:	3CN3
Amyloid Category:	Non-amyloid
Type:	Inhibitor complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	Hormone
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.8
R free:	0.21600000

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
LJ4	A	C12 H8 Br2 O2	344.0	2,6-dibromo-4-phenoxyphenol	c1ccc(cc1)Oc2cc(c(c(c2)Br)O)Br	CRSZEDOZGJPOHP-UHFFFAOYSA-N
LJ4	B	C12 H8 Br2 O2	344.0	2,6-dibromo-4-phenoxyphenol	c1ccc(cc1)Oc2cc(c(c(c2)Br)O)Br	CRSZEDOZGJPOHP-UHFFFAOYSA-N

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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) in complex with N-(3,5-Dibromo-4-hydroxyphenyl)benzamide

To develop potent and highly selective transthyretin (TTR) amyloidogenesis inhibitors, it is useful to systematically optimize the three substructural elements that compose a typical TTR kinetic stabilizer: the two aryl rings and the linker joining them. They have evaluated bisaryl molecules with linker substructures to determine how these linkages influence inhibitor potency and selectivity. These linkers connect one unsubstituted aromatic ring to either a 3,5-X 2 or a 3,5-X 2-4-OH phenyl substructure (X = Br or CH 3).

Literature

PMID:	18811132
Author(s):	Johnson, S.M., Connelly, S., Wilson, I.A., Kelly, J.W.
Reference:	J Med Chem. 2008 Oct 23;51(20):6348-58.

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:	3CN4
Amyloid Category:	Non-amyloid
Type:	Inhibitor complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	Hormone
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.4
R free:	0.20199999

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
LJ5	A	C13 H9 Br2 N O2	371.02	N-(3,5-dibromo-4-hydroxyphenyl)benzamide	c1ccc(cc1)C(=O)Nc2cc(c(c(c2)Br)O)Br	HKODPZBPODONGO-UHFFFAOYSA-N
LJ5	B	C13 H9 Br2 N O2	371.02	N-(3,5-dibromo-4-hydroxyphenyl)benzamide	c1ccc(cc1)C(=O)Nc2cc(c(c(c2)Br)O)Br	HKODPZBPODONGO-UHFFFAOYSA-N

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

L

S

P

Y

S

Y

S

T

A

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 diflunisal

Analogues of diflunisal, an FDA-approved nonsteroidal antiinflammatory drug (NSAID), were synthesized and evaluated as inhibitors of transthyretin (TTR) aggregation, including amyloid fibril formation. Biophysical studies reveal that inhibitors dramatically slow tetramer dissociation (the rate-determining step of amyloidogenesis) over a duration of 168 h. This appears to be achieved through ground-state stabilization, which raises the kinetic barrier for tetramer dissociation.

Literature

PMID:	14711308
Author(s):	Adamski-Werner, S.L., Palaninathan, S.K., Sacchettini, J.C., Kelly, J.W.
Reference:	J Med Chem. 2004 Jan 15;47(2):355-74

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:	3D2T
Amyloid Category:	Non-amyloid
Type:	Inhibitor complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	HORMONE
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.85
R free:	0.235

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
1FL	A	C13 H8 F2 O3	250.2	5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID	c1cc(c(cc1c2ccc(cc2F)F)C(=O)O)O	HUPFGZXOMWLGNK-UHFFFAOYSA-N
1FL	B	C13 H8 F2 O3	250.2	5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID	c1cc(c(cc1c2ccc(cc2F)F)C(=O)O)O	HUPFGZXOMWLGNK-UHFFFAOYSA-N

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

M

H

E

H

A

E

V

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

M

L

S

P

Y

S

Y

S

T

A

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

M

H

E

H

A

E

V

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

M

L

S

P

Y

S

Y

S

T

A

V

T

N

P

125

126

K

E

127

Chain 3

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

M

H

E

H

A

E

V

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

M

L

S

P

Y

S

Y

S

T

A

V

T

N

P

125

126

K

E

127

Chain 4

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

D

T

W

E

P

F

A

S

G

K

T

S

50

51

E

S

G

E

L

H

G

L

T

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

M

H

E

H

A

E

V

F

T

A

N

D

S

100

101

G

P

R

Y

T

I

A

M

L

S

P

Y

S

Y

S

T

A

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

Crystal structure of the F87M/L110M mutant of human transthyretin at pH 4.6

They report the first crystal structure of human TTR in complex with Zn(2+) at pH 4.6-7.5. All four structures reveal three tetra-coordinated Zn(2+)-binding sites (ZBS 1-3) per monomer, plus a fourth site (ZBS 4) involving amino acid residues from a symmetry-related tetramer that is not visible in solution by NMR. Stability of the monomer of TTR decreases in the presence of Zn(2+), which is consistent with the tertiary structural perturbation provoked by Zn(2+) binding, tetramer stability is only marginally affected by Zn(2+). These data highlight structural and functional roles of Zn(2+) in TTR-related amyloidoses.

Literature

PMID:	20659897
Author(s):	Palmieri, L.de.C., Lima, L.M., Freire, J.B., Bleicher, L., Polikarpov, I., Almeida, F.C., Foguel, D.
Reference:	J Biol Chem. 2010 Oct 8;285(41):31731-41.

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):	F87M/L110M
E.C. Number:
UniProt ID:	P02766
Keyword(s):	Transthyretin

Structure Information

PDB ID:	3DGD
Amyloid Category:	Amyloid
Type:	Aggregating complex
Global Stoichiometry:	Homo 4-mer - A4
PDB Classification:	TRANSPORT PROTEIN
Method:	X-RAY DIFFRACTION
Resolution (Å):	1.383
R free:	0.20199999

Ligand Information

Ligand ID	Chain ID	Ligand Formula	Ligand MW	Ligand Name	Ligand SMILES	InChI Key
ACT	A	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
ZN	A	Zn 2	65.41	ZINC ION	[Zn+2]	PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT	B	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
GOL	B	C3 H8 O3	92.09	GLYCEROL	C(C(CO)O)O	PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN	B	Zn 2	65.41	ZINC ION	[Zn+2]	PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT	C	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
ZN	C	Zn 2	65.41	ZINC ION	[Zn+2]	PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT	D	C2 H3 O2 -1	59.04	ACETATE ION	CC(=O)[O-]	QTBSBXVTEAMEQO-UHFFFAOYSA-M
GOL	D	C3 H8 O3	92.09	GLYCEROL	C(C(CO)O)O	PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN	D	Zn 2	65.41	ZINC ION	[Zn+2]	PTFCDOFLOPIGGS-UHFFFAOYSA-N

Structure database of aggregation related proteins and peptides

Displaying 181 to 210 records out of 565 records fetched.

PMID:	18395224
Author(s):	Esposito, G., Ricagno, S., Corazza, A., Rennella, E., Gumral, D., Mimmi, M.C., Betto, E., Pucillo, C.E.M., Fogolari, F., Viglino, P., Raimondi, S., Giorgetti, S., Bolognesi, B., Merlini, G., Stoppini, M., Bolognesi, M., Bellotti, V.
Reference:	J Mol Biol. 2008 May 9;378(4):887-97.