2h4e
From Proteopedia
(New page: 200px<br /> <applet load="2h4e" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h4e, resolution 1.45Å" /> '''Crystal structure o...) |
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| - | [[Image:2h4e.gif|left|200px]]<br /> | + | [[Image:2h4e.gif|left|200px]]<br /><applet load="2h4e" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2h4e, resolution 1.45Å" /> | caption="2h4e, resolution 1.45Å" /> | ||
'''Crystal structure of Cys10 sulfonated transthyretin'''<br /> | '''Crystal structure of Cys10 sulfonated transthyretin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Transthyretin (TTR) is a plasma protein, which under conditions not yet | + | Transthyretin (TTR) is a plasma protein, which under conditions not yet completely understood, aggregates forming amyloid deposits that occur extracellularly. It is a protein composed of four identical subunits. Each monomer has a single cysteine residue (Cys10), which in the plasma is reduced (Cys-SH), oxidized (Cys-SO3-), sulfonated (Cys-S-SO3-) or bound to various sulfhydryls. There is evidence that these chemical modifications of the SH group alter the stability and the amyloidogenic potential of the protein. The sulfonated form was found to enhance the stability of the native conformation of TTR, avoiding misassembly of the protein leading to amyloid. Consequently, the potential treatment of TTR-type amyloidosis by sulfite has been suggested. The structure of TTR pre-incubated with sulfite at physiological pH, was determined by X-ray crystallography to provide structural insight for the stabilizing effect of sulfite. Each subunit has a beta-sandwich conformation, with two four stranded beta-pleated sheets (DAGH and CBEF) and a small alpha-helix between strands. The sulfonated cysteines have two sulfite oxygens involved in intramonomer hydrogen bonds that bridge Cys10, the amino acid immediately before beta-strand A, to the amino acids immediately after the edge beta-strand D. Implications of the newly observed interactions in the inhibition of fibril formation are discussed in light of the recent structural models of TTR amyloid fibrils. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2H4E 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 SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2H4E 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=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H4E OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Damas, A | + | [[Category: Damas, A M.]] |
[[Category: Gales, L.]] | [[Category: Gales, L.]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: transthyretin]] | [[Category: transthyretin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:38:06 2008'' |
Revision as of 15:38, 21 February 2008
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Crystal structure of Cys10 sulfonated transthyretin
Contents |
Overview
Transthyretin (TTR) is a plasma protein, which under conditions not yet completely understood, aggregates forming amyloid deposits that occur extracellularly. It is a protein composed of four identical subunits. Each monomer has a single cysteine residue (Cys10), which in the plasma is reduced (Cys-SH), oxidized (Cys-SO3-), sulfonated (Cys-S-SO3-) or bound to various sulfhydryls. There is evidence that these chemical modifications of the SH group alter the stability and the amyloidogenic potential of the protein. The sulfonated form was found to enhance the stability of the native conformation of TTR, avoiding misassembly of the protein leading to amyloid. Consequently, the potential treatment of TTR-type amyloidosis by sulfite has been suggested. The structure of TTR pre-incubated with sulfite at physiological pH, was determined by X-ray crystallography to provide structural insight for the stabilizing effect of sulfite. Each subunit has a beta-sandwich conformation, with two four stranded beta-pleated sheets (DAGH and CBEF) and a small alpha-helix between strands. The sulfonated cysteines have two sulfite oxygens involved in intramonomer hydrogen bonds that bridge Cys10, the amino acid immediately before beta-strand A, to the amino acids immediately after the edge beta-strand D. Implications of the newly observed interactions in the inhibition of fibril formation are discussed in light of the recent structural models of TTR amyloid fibrils.
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
2H4E is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for the protective role of sulfite against transthyretin amyloid formation., Gales L, Saraiva MJ, Damas AM, Biochim Biophys Acta. 2007 Jan;1774(1):59-64. Epub 2006 Nov 6. PMID:17175208
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