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2b16
From Proteopedia
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| - | [[Image:2b16.gif|left|200px]] | + | [[Image:2b16.gif|left|200px]] |
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| - | '''The crystal structure of 2,4-dinitrophenol in complex with the amyloidogenic variant Transthyretin Tyr78Phe''' | + | {{Structure |
| + | |PDB= 2b16 |SIZE=350|CAPTION= <scene name='initialview01'>2b16</scene>, resolution 1.75Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=DNF:2,4-DINITROPHENOL'>DNF</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''The crystal structure of 2,4-dinitrophenol in complex with the amyloidogenic variant Transthyretin Tyr78Phe''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2B16 is a [ | + | 2B16 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B16 OCA]. |
==Reference== | ==Reference== | ||
| - | The binding of 2,4-dinitrophenol to wild-type and amyloidogenic transthyretin., Morais-de-Sa E, Neto-Silva RM, Pereira PJ, Saraiva MJ, Damas AM, Acta Crystallogr D Biol Crystallogr. 2006 May;62(Pt 5):512-9. Epub 2006, Apr 19. PMID:[http:// | + | The binding of 2,4-dinitrophenol to wild-type and amyloidogenic transthyretin., Morais-de-Sa E, Neto-Silva RM, Pereira PJ, Saraiva MJ, Damas AM, Acta Crystallogr D Biol Crystallogr. 2006 May;62(Pt 5):512-9. Epub 2006, Apr 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16627944 16627944] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: transthyretin]] | [[Category: transthyretin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:56:21 2008'' |
Revision as of 13:56, 20 March 2008
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| , resolution 1.75Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
The crystal structure of 2,4-dinitrophenol in complex with the amyloidogenic variant Transthyretin Tyr78Phe
Contents |
Overview
Systemic deposition of transthyretin (TTR) amyloid fibrils is always observed in familial amyloidotic polyneuropathy, senile systemic amyloidosis and familial amyloidotic cardiomyopathy patients. Destabilization of the molecule leads to a cascade of events which result in fibril formation. The destabilization of a native protein with consequent conformational changes appears to be a common link in several human amyloid diseases. Intensive research has been directed towards finding small molecules that could work as therapeutic agents for the prevention/inhibition of amyloid diseases through stabilization of the native fold of the potentially amyloidogenic protein. This work provides insight into the structural determinants of the highly stabilizing effects of 2,4-dinitrophenol on wild-type TTR. It is also shown that similar interactions are established between this molecule and two highly amyloidogenic TTR variants: TTR L55P and TTR Y78F. In the three crystal complexes, 2,4-dinitrophenol occupies the two hormone-binding sites of the TTR tetramer. As a result of 2,4-dinitrophenol binding, the two dimers in the TTR tetramer become closer, increasing the stability of the protein. The three-dimensional structures now determined allow a comprehensive description of key interactions between transthyretin and 2,4-dinitrophenol, a small compound that holds promise as a template for the design of a therapeutical drug for amyloid diseases.
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
2B16 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The binding of 2,4-dinitrophenol to wild-type and amyloidogenic transthyretin., Morais-de-Sa E, Neto-Silva RM, Pereira PJ, Saraiva MJ, Damas AM, Acta Crystallogr D Biol Crystallogr. 2006 May;62(Pt 5):512-9. Epub 2006, Apr 19. PMID:16627944
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