2gab

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{{STRUCTURE_2gab| PDB=2gab | SCENE= }}
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==Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4-hydroxy-3,3',5,4'-tetrachlorobiphenyl==
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===Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4-hydroxy-3,3',5,4'-tetrachlorobiphenyl===
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<StructureSection load='2gab' size='340' side='right' caption='[[2gab]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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{{ABSTRACT_PUBMED_15610856}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2gab]] is a 2 chain structure with 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=2GAB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GAB FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NE2:3,3,4,5-TETRACHLOROBIPHENYL-4-OL'>NE2</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TTR, PALB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gab OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gab RCSB], [http://www.ebi.ac.uk/pdbsum/2gab PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN]] Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:[http://omim.org/entry/105210 105210]]. A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor.<ref>PMID:11243784</ref> <ref>PMID:15735344</ref> <ref>PMID:19167329</ref> <ref>PMID:3818577</ref> <ref>PMID:3022108</ref> <ref>PMID:6651852</ref> <ref>PMID:6583672</ref> <ref>PMID:3135807</ref> <ref>PMID:1517749</ref> <ref>PMID:1932142</ref> <ref>PMID:7923855</ref> <ref>PMID:8382610</ref> <ref>PMID:8428915</ref> <ref>PMID:9733771</ref> <ref>PMID:12403615</ref> <ref>PMID:16185074</ref> <ref>PMID:16627944</ref> <ref>PMID:6487335</ref> <ref>PMID:3722385</ref> <ref>PMID:2891727</ref> <ref>PMID:2161654</ref> <ref>PMID:2363717</ref> <ref>PMID:1656975</ref> <ref>PMID:2046936</ref> <ref>PMID:1570831</ref> <ref>PMID:1734866</ref> <ref>PMID:1520326</ref> <ref>PMID:1520336</ref> <ref>PMID:1544214</ref> <ref>PMID:1351039</ref> <ref>PMID:1301926</ref> <ref>PMID:1362222</ref> <ref>PMID:1436517</ref> <ref>PMID:8352764</ref> <ref>PMID:8038017</ref> <ref>PMID:8257997</ref> <ref>PMID:8095302</ref> <ref>PMID:1997217</ref> <ref>PMID:8019560</ref> <ref>PMID:8081397</ref> <ref>PMID:7914929</ref> <ref>PMID:8133316</ref> <ref>PMID:7910950</ref> <ref>PMID:7655883</ref> <ref>PMID:7850982</ref> <ref>PMID:8579098</ref> <ref>PMID:9066351</ref> <ref>PMID:8990019</ref> <ref>PMID:9605286</ref> <ref>PMID:10036587</ref> <ref>PMID:10627135</ref> <ref>PMID:10694917</ref> <ref>PMID:10211412</ref> <ref>PMID:10439117</ref> <ref>PMID:10611950</ref> <ref>PMID:10071047</ref> <ref>PMID:10436378</ref> <ref>PMID:10842705</ref> <ref>PMID:10842718</ref> <ref>PMID:10882995</ref> <ref>PMID:11445644</ref> <ref>PMID:12557757</ref> <ref>PMID:11866053</ref> <ref>PMID:12050338</ref> <ref>PMID:12771253</ref> <ref>PMID:15214015</ref> <ref>PMID:15478468</ref> <ref>PMID:15217993</ref> <ref>PMID:17453626</ref> <ref>PMID:17577687</ref> <ref>PMID:17503405</ref> <ref>PMID:17635579</ref> Defects in TTR are a cause of hyperthyroxinemia dystransthyretinemic euthyroidal (HTDE) [MIM:[http://omim.org/entry/145680 145680]]. It is a condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities.<ref>PMID:1979335</ref> Defects in TTR are a cause of carpal tunnel syndrome type 1 (CTS1) [MIM:[http://omim.org/entry/115430 115430]]. It is a condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis.<ref>PMID:8309582</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN]] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.<ref>PMID:3714052</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ga/2gab_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) are known to bind to transthyretin (TTR) in vitro, possibly explaining their bioaccumulation, rodent toxicity, and presumed human toxicity. Herein, we show that several OH-PCBs bind selectively to TTR in blood plasma; however, only one of the PCBs tested binds TTR in plasma. Some of the OH-PCBs displace thyroid hormone (T4) from TTR, rationalizing the toxicity observed in rodents, where TTR is the major T4 transporter. Thyroid binding globulin and albumin are the major T4 carriers in humans, making it unlikely that enough T4 could be displaced from TTR to be toxic. OH-PCBs are excellent TTR amyloidogenesis inhibitors in vitro because they bind to the TTR tetramer, imparting kinetic stability under amyloidogenic denaturing conditions. Four OH-PCB/TTR cocrystal structures provide further insight into inhibitor binding interactions.
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==Disease==
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Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity.,Purkey HE, Palaninathan SK, Kent KC, Smith C, Safe SH, Sacchettini JC, Kelly JW Chem Biol. 2004 Dec;11(12):1719-28. PMID:15610856<ref>PMID:15610856</ref>
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[[http://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN]] Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:[http://omim.org/entry/105210 105210]]. A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor.<ref>PMID:11243784</ref><ref>PMID:15735344</ref><ref>PMID:19167329</ref><ref>PMID:3818577</ref><ref>PMID:3022108</ref><ref>PMID:6651852</ref><ref>PMID:6583672</ref><ref>PMID:3135807</ref><ref>PMID:1517749</ref><ref>PMID:1932142</ref><ref>PMID:7923855</ref><ref>PMID:8382610</ref><ref>PMID:8428915</ref><ref>PMID:9733771</ref><ref>PMID:12403615</ref><ref>PMID:16185074</ref><ref>PMID:16627944</ref><ref>PMID:6487335</ref><ref>PMID:3722385</ref><ref>PMID:2891727</ref><ref>PMID:2161654</ref><ref>PMID:2363717</ref><ref>PMID:1656975</ref><ref>PMID:2046936</ref><ref>PMID:1570831</ref><ref>PMID:1734866</ref><ref>PMID:1520326</ref><ref>PMID:1520336</ref><ref>PMID:1544214</ref><ref>PMID:1351039</ref><ref>PMID:1301926</ref><ref>PMID:1362222</ref><ref>PMID:1436517</ref><ref>PMID:8352764</ref><ref>PMID:8038017</ref><ref>PMID:8257997</ref><ref>PMID:8095302</ref><ref>PMID:1997217</ref><ref>PMID:8019560</ref><ref>PMID:8081397</ref><ref>PMID:7914929</ref><ref>PMID:8133316</ref><ref>PMID:7910950</ref><ref>PMID:7655883</ref><ref>PMID:7850982</ref><ref>PMID:8579098</ref><ref>PMID:9066351</ref><ref>PMID:8990019</ref><ref>PMID:9605286</ref><ref>PMID:10036587</ref><ref>PMID:10627135</ref><ref>PMID:10694917</ref><ref>PMID:10211412</ref><ref>PMID:10439117</ref><ref>PMID:10611950</ref><ref>PMID:10071047</ref><ref>PMID:10436378</ref><ref>PMID:10842705</ref><ref>PMID:10842718</ref><ref>PMID:10882995</ref><ref>PMID:11445644</ref><ref>PMID:12557757</ref><ref>PMID:11866053</ref><ref>PMID:12050338</ref><ref>PMID:12771253</ref><ref>PMID:15214015</ref><ref>PMID:15478468</ref><ref>PMID:15217993</ref><ref>PMID:17453626</ref><ref>PMID:17577687</ref><ref>PMID:17503405</ref><ref>PMID:17635579</ref> Defects in TTR are a cause of hyperthyroxinemia dystransthyretinemic euthyroidal (HTDE) [MIM:[http://omim.org/entry/145680 145680]]. It is a condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities.<ref>PMID:1979335</ref> Defects in TTR are a cause of carpal tunnel syndrome type 1 (CTS1) [MIM:[http://omim.org/entry/115430 115430]]. It is a condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis.<ref>PMID:8309582</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN]] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.<ref>PMID:3714052</ref>
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</div>
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==About this Structure==
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[[2gab]] is a 2 chain structure with 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=2GAB OCA].
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==See Also==
==See Also==
*[[Transthyretin|Transthyretin]]
*[[Transthyretin|Transthyretin]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015610856</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Kelly, J W.]]
[[Category: Kelly, J W.]]

Revision as of 08:23, 30 September 2014

Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4-hydroxy-3,3',5,4'-tetrachlorobiphenyl

2gab, resolution 1.85Å

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