5l4m

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'''Unreleased structure'''
 
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The entry 5l4m is ON HOLD
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==Crystal Structure of Human Transthyretin in Complex with 3,5,6-Trichloro-2-pyridinyloxyacetic acid (Triclopyr)==
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<StructureSection load='5l4m' size='340' side='right'caption='[[5l4m]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5l4m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L4M FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.581&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SBK:TRICLOPYR'>SBK</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5l4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l4m OCA], [https://pdbe.org/5l4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l4m RCSB], [https://www.ebi.ac.uk/pdbsum/5l4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l4m ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN] Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:[https://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:[https://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:[https://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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[https://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 style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Thyroid disruption by xenobiotics is associated with a broad spectrum of severe adverse outcomes. One possible molecular target of thyroid hormone disrupting chemicals (THDCs) is transthyretin (TTR), a thyroid hormone transporter in vertebrates. To better understand the interactions between TTR and THDCs, we determined the crystallographic structures of human TTR in complex with perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2,2',4,4'-tetrahydroxybenzophenone (BP2). The molecular interactions between the ligands and TTR were further characterized using molecular dynamics simulations. A structure-based virtual screening (VS) protocol was developed with the intention of providing an efficient tool for the discovery of novel TTR binders from the Tox21 inventory. Among the 192 predicted binders, twelve representatives were selected and their TTR binding affinities were studied with isothermal titration calorimetry, of which seven compounds had binding affinities between 0.26-100 muM. To elucidate structural details in their binding to TTR, crystal structures were determined of TTR in complex with four of the identified compounds including 2,6-dinitro-p-cresol, bisphenol S, clonixin and triclopyr. The compounds were found to bind in the TTR hormone binding sites as predicted. Our results show that the developed VS protocol is able to successfully identify potential THDCs and we suggest that it can be used to propose THDCs for future toxicological evaluations.
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Authors: Grundstrom, C., Hall, M., Zhang, J., Olofsson, A., Andersson, P., Sauer-Eriksson, A.E.
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A Structure-based Virtual Screening Protocol for in silico Identification of Potential Thyroid Disrupting Chemicals Targeting Transthyretin.,Zhang J, Begum A, Brannstrom K, Grundstrom C, Iakovleva I, Olofsson A, Sauer-Eriksson AE, Andersson PL Environ Sci Technol. 2016 Sep 26. PMID:27668830<ref>PMID:27668830</ref>
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Description: Crystal Structure of Human Transthyretin in Complex with 3,5,6-Trichloro-2-pyridinyloxyacetic acid (Triclopyr)
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Sauer-Eriksson, A.E]]
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<div class="pdbe-citations 5l4m" style="background-color:#fffaf0;"></div>
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[[Category: Grundstrom, C]]
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[[Category: Hall, M]]
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==See Also==
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[[Category: Olofsson, A]]
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*[[Transthyretin 3D structures|Transthyretin 3D structures]]
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[[Category: Zhang, J]]
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== References ==
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[[Category: Andersson, P]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Andersson P]]
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[[Category: Grundstrom C]]
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[[Category: Hall M]]
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[[Category: Olofsson A]]
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[[Category: Sauer-Eriksson AE]]
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[[Category: Zhang J]]

Current revision

Crystal Structure of Human Transthyretin in Complex with 3,5,6-Trichloro-2-pyridinyloxyacetic acid (Triclopyr)

PDB ID 5l4m

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