2h4e
From Proteopedia
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|PDB= 2h4e |SIZE=350|CAPTION= <scene name='initialview01'>2h4e</scene>, resolution 1.45Å | |PDB= 2h4e |SIZE=350|CAPTION= <scene name='initialview01'>2h4e</scene>, resolution 1.45Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=CSU:CYSTEINE-S-SULFONIC+ACID'>CSU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= TTR, PALB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TTR, PALB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h4e OCA], [http://www.ebi.ac.uk/pdbsum/2h4e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h4e RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Amyloidosis, senile systemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Carpal tunnel syndrome, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Dystransthyretinemic hyperthyroxinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Damas, A M.]] | [[Category: Damas, A M.]] | ||
[[Category: Gales, L.]] | [[Category: Gales, L.]] | ||
| - | [[Category: SO4]] | ||
[[Category: amyloid]] | [[Category: amyloid]] | ||
[[Category: familial amyloidotic polyneuropathy]] | [[Category: familial amyloidotic polyneuropathy]] | ||
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[[Category: transthyretin]] | [[Category: transthyretin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:25:17 2008'' |
Revision as of 00:25, 31 March 2008
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| , resolution 1.45Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | TTR, PALB (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Cys10 sulfonated transthyretin
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.
About this Structure
2H4E is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Mon Mar 31 03:25:17 2008
