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| [[Image:2b14.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2b14| PDB=2b14 | SCENE= }} | | {{STRUCTURE_2b14| PDB=2b14 | SCENE= }} |
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| '''The crystal structure of 2,4-dinitrophenol in complex with the amyloidogenic variant Transthyretin Leu 55 Pro'''
| | ===The crystal structure of 2,4-dinitrophenol in complex with the amyloidogenic variant Transthyretin Leu 55 Pro=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16627944}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16627944 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16627944}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Tetramer stabilizer]] | | [[Category: Tetramer stabilizer]] |
| [[Category: Transthyretin]] | | [[Category: Transthyretin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:43:24 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:19:46 2008'' |
