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1z7j

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(New page: 200px<br /> <applet load="1z7j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z7j, resolution 2.20&Aring;" /> '''Human transthyretin...)
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<applet load="1z7j" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Human transthyretin (also called prealbumin) complex with 3, 3',5,5'-tetraiodothyroacetic acid (t4ac)'''<br />
'''Human transthyretin (also called prealbumin) complex with 3, 3',5,5'-tetraiodothyroacetic acid (t4ac)'''<br />
==Overview==
==Overview==
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The crystal structure of the complex of human transthyretin (hTTR) with, 3,3',5,5'-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2, Angstrom resolution. The complex crystallizes in the orthorhombic space, group P2(1)2(1)2, with unit-cell parameters a = 43.46, b = 85.85, c =, 65.44 Angstrom. The structure was refined to R = 17.3% and R(free) = 21.9%, for reflections without any sigma-cutoff. T4Ac is bound in both the, forward and the reverse mode in the two binding sites of hTTR. In the, forward orientation, T4Ac binds in a position similar to that described, for thyroxine (T4) in the orthorhombic hTTR-T4 complex. In this, orientation, the iodine substituents of the phenolic ring are bound in the, P3'/P2 halogen pockets. In the reverse orientation, which is the major, binding mode of T4Ac, the ligand is bound deep in the TTR channel, with, the carboxylic group bound in the P3' pocket and forming simultaneous, polar interactions with the residues constituting the two hormone-binding, sites. Such interactions of a thyroxine-analogue ligand bound in the, reverse mode have never been observed in TTR complexes previously.
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The crystal structure of the complex of human transthyretin (hTTR) with 3,3',5,5'-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2 Angstrom resolution. The complex crystallizes in the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 43.46, b = 85.85, c = 65.44 Angstrom. The structure was refined to R = 17.3% and R(free) = 21.9% for reflections without any sigma-cutoff. T4Ac is bound in both the forward and the reverse mode in the two binding sites of hTTR. In the forward orientation, T4Ac binds in a position similar to that described for thyroxine (T4) in the orthorhombic hTTR-T4 complex. In this orientation, the iodine substituents of the phenolic ring are bound in the P3'/P2 halogen pockets. In the reverse orientation, which is the major binding mode of T4Ac, the ligand is bound deep in the TTR channel, with the carboxylic group bound in the P3' pocket and forming simultaneous polar interactions with the residues constituting the two hormone-binding sites. Such interactions of a thyroxine-analogue ligand bound in the reverse mode have never been observed in TTR complexes previously.
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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1Z7J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with T4A as [http://en.wikipedia.org/wiki/ligand ligand]. This structure superseeds the now removed PDB entry 1KED. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Z7J OCA].
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1Z7J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=T4A:'>T4A</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 1KED. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z7J OCA].
==Reference==
==Reference==
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[[Category: vitamin a]]
[[Category: vitamin a]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:30:37 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:50 2008''

Revision as of 14:12, 21 February 2008


1z7j, resolution 2.20Å

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Human transthyretin (also called prealbumin) complex with 3, 3',5,5'-tetraiodothyroacetic acid (t4ac)

Contents

Overview

The crystal structure of the complex of human transthyretin (hTTR) with 3,3',5,5'-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2 Angstrom resolution. The complex crystallizes in the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 43.46, b = 85.85, c = 65.44 Angstrom. The structure was refined to R = 17.3% and R(free) = 21.9% for reflections without any sigma-cutoff. T4Ac is bound in both the forward and the reverse mode in the two binding sites of hTTR. In the forward orientation, T4Ac binds in a position similar to that described for thyroxine (T4) in the orthorhombic hTTR-T4 complex. In this orientation, the iodine substituents of the phenolic ring are bound in the P3'/P2 halogen pockets. In the reverse orientation, which is the major binding mode of T4Ac, the ligand is bound deep in the TTR channel, with the carboxylic group bound in the P3' pocket and forming simultaneous polar interactions with the residues constituting the two hormone-binding sites. Such interactions of a thyroxine-analogue ligand bound in the reverse mode have never been observed in TTR complexes previously.

Disease

Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]

About this Structure

1Z7J is a Single protein structure of sequence from Homo sapiens with as ligand. This structure supersedes the now removed PDB entry 1KED. Full crystallographic information is available from OCA.

Reference

Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolution., Neumann P, Cody V, Wojtczak A, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1313-9. Epub 2005, Sep 28. PMID:16204882

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