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1z7j

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(New page: 200px<br /> <applet load="1z7j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z7j, resolution 2.20&Aring;" /> '''Human transthyretin...)
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[[Image:1z7j.gif|left|200px]]<br />
 
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<applet load="1z7j" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1z7j, resolution 2.20&Aring;" />
 
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'''Human transthyretin (also called prealbumin) complex with 3, 3',5,5'-tetraiodothyroacetic acid (t4ac)'''<br />
 
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==Overview==
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==Human transthyretin (also called prealbumin) complex with 3, 3',5,5'-tetraiodothyroacetic acid (t4ac)==
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The crystal structure of the complex of human transthyretin (hTTR) with, 3,3',5,5'-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2, Angstrom resolution. The complex crystallizes in the orthorhombic space, group P2(1)2(1)2, with unit-cell parameters a = 43.46, b = 85.85, c =, 65.44 Angstrom. The structure was refined to R = 17.3% and R(free) = 21.9%, for reflections without any sigma-cutoff. T4Ac is bound in both the, forward and the reverse mode in the two binding sites of hTTR. In the, forward orientation, T4Ac binds in a position similar to that described, for thyroxine (T4) in the orthorhombic hTTR-T4 complex. In this, orientation, the iodine substituents of the phenolic ring are bound in the, P3'/P2 halogen pockets. In the reverse orientation, which is the major, binding mode of T4Ac, the ligand is bound deep in the TTR channel, with, the carboxylic group bound in the P3' pocket and forming simultaneous, polar interactions with the residues constituting the two hormone-binding, sites. Such interactions of a thyroxine-analogue ligand bound in the, reverse mode have never been observed in TTR complexes previously.
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<StructureSection load='1z7j' size='340' side='right'caption='[[1z7j]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1z7j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1ked 1ked]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z7J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z7J 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]] 2.2&#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=T4A:3,3,5,5-TETRAIODOTHYROACETIC+ACID'>T4A</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=1z7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z7j OCA], [https://pdbe.org/1z7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z7j RCSB], [https://www.ebi.ac.uk/pdbsum/1z7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z7j 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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== 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/z7/1z7j_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/main_output.php?pdb_ID=1z7j 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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The crystal structure of the complex of human transthyretin (hTTR) with 3,3',5,5'-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2 Angstrom resolution. The complex crystallizes in the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 43.46, b = 85.85, c = 65.44 Angstrom. The structure was refined to R = 17.3% and R(free) = 21.9% for reflections without any sigma-cutoff. T4Ac is bound in both the forward and the reverse mode in the two binding sites of hTTR. In the forward orientation, T4Ac binds in a position similar to that described for thyroxine (T4) in the orthorhombic hTTR-T4 complex. In this orientation, the iodine substituents of the phenolic ring are bound in the P3'/P2 halogen pockets. In the reverse orientation, which is the major binding mode of T4Ac, the ligand is bound deep in the TTR channel, with the carboxylic group bound in the P3' pocket and forming simultaneous polar interactions with the residues constituting the two hormone-binding sites. Such interactions of a thyroxine-analogue ligand bound in the reverse mode have never been observed in TTR complexes previously.
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==Disease==
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Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolution.,Neumann P, Cody V, Wojtczak A Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1313-9. Epub 2005, Sep 28. PMID:16204882<ref>PMID:16204882</ref>
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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]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1Z7J 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 T4A as [http://en.wikipedia.org/wiki/ligand ligand]. This structure superseeds the now removed PDB entry 1KED. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Z7J OCA].
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</div>
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<div class="pdbe-citations 1z7j" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolution., Neumann P, Cody V, Wojtczak A, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1313-9. Epub 2005, Sep 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16204882 16204882]
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*[[Transthyretin 3D structures|Transthyretin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Cody, V.]]
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[[Category: Cody V]]
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[[Category: Neumann, P.]]
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[[Category: Neumann P]]
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[[Category: Wojtczak, A.]]
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[[Category: Wojtczak A]]
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[[Category: T4A]]
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[[Category: albumin]]
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[[Category: amyloid]]
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[[Category: cerebrospinal fluid]]
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[[Category: disease mutation]]
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[[Category: liver]]
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[[Category: plasma]]
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[[Category: polymorphism]]
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[[Category: polyneuropathy]]
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[[Category: prealbumin]]
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[[Category: retinol-binding]]
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[[Category: t4ac]]
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[[Category: tetraiodothyroacetic acid]]
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[[Category: thyroid hormone]]
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[[Category: transport]]
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[[Category: vitamin a]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:30:37 2007''
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Current revision

Human transthyretin (also called prealbumin) complex with 3, 3',5,5'-tetraiodothyroacetic acid (t4ac)

PDB ID 1z7j

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