2roy: Difference between revisions

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-[[Image:2roy.gif|left|200px]]<br />
-<applet load="2roy" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2roy, resolution 2.2&Aring;" />
-'''TRANSTHYRETIN (ALSO CALLED PREALBUMIN) COMPLEX WITH 3',5'-DINITRO-N-ACETYL-L-THYRONINE'''<br />
-==Overview==
+==TRANSTHYRETIN (ALSO CALLED PREALBUMIN) COMPLEX WITH 3',5'-DINITRO-N-ACETYL-L-THYRONINE==
-The molecular structures of two human transthyretin (hTTR, prealbumin), complexes, co-crystallized with thyroxine, (3,5,3',5'-tetraiodo-L-thyronine; T(4)), and with, 3',5'-dinitro-N-acetyl-LL-thyronine (DNNAT), were determined by X-ray, diffraction methods. Crystals of both structures are orthorhombic, space, group P2(1)2(1)2, and have two independent monomers in the asymmetric unit, of the crystal lattice. These structures have been refined to 17.0% for, 8-2.0 A resolution data for the T(4) complex (I), and to R = 18.4% for, 8-2.2 A resolution data for the DNNAT structure (II). This report provides, a detailed description of T(4) binding to wild-type hTTR at 2.0 A, resolution, as well as DNNAT. In both structures, the two independent, hormone-binding sites of the TTR tetramer are occupied by ligand. A 50%, statistical disorder model was applied to account for the crystallographic, twofold symmetry along the binding channel and the lack of such symmetry, for the ligands. Results for the co-crystallized T(4) complex show that, T(4) binds deep in the hormone-binding channel and displaces the bound, water previously reported for T(4) soaked into a native transthyretin, crystal [Blake &amp; Oatley (1977). Nature (London), 268, 115-120]. DNNAT also, binds deeper in the channel toward the tetramer center than T(4) with the, nitro groups occupying the symmetrical innermost halogen pockets. The, N-acetyl moiety does not form polar contacts with the protein side chains, as it is oriented toward the center of the channel. The weak binding, affinity of DNNAT results from the loss of hydrophobic interactions with, the halogen binding pockets as observed in T(4) binding. These data, suggest that the halogen-binding sites toward the tetramer center are of, primary importance as they are occupied by analogues with weak affinity to, TTR, and are therefore selected over the other halogen sites which, contribute more strongly to the overall binding affinity.
+<StructureSection load='2roy' size='340' side='right'caption='[[2roy]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2roy]] 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=1roy 1roy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ROY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ROY FirstGlance]. <br>
+</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>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P28:3,5-DINITRO-N-ACETYL-L-THYRONINE'>P28</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2roy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2roy OCA], [https://pdbe.org/2roy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2roy RCSB], [https://www.ebi.ac.uk/pdbsum/2roy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2roy ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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>
+== Function ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ro/2roy_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2roy ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-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]]
+*[[Transthyretin 3D structures|Transthyretin 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-ROY 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 P28 as [http://en.wikipedia.org/wiki/ligand ligand]. This structure superseeds the now removed PDB entry 1ROY. Structure known Active Sites: A1 and B1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2ROY OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Structures of human transthyretin complexed with thyroxine at 2.0 A resolution and 3',5'-dinitro-N-acetyl-L-thyronine at 2.2 A resolution., Wojtczak A, Cody V, Luft JR, Pangborn W, Acta Crystallogr D Biol Crystallogr. 1996 Jul 1;52(Pt 4):758-65. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15299640 15299640]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Cody, V.]]
+[[Category: Cody V]]
-[[Category: Luft, J.R.]]
+[[Category: Luft JR]]
-[[Category: Pangborn, W.]]
+[[Category: Pangborn W]]
-[[Category: Wojtczak, A.]]
+[[Category: Wojtczak A]]
-[[Category: P28]]
-[[Category: albumin]]
-[[Category: amyloid]]
-[[Category: cerebrospinal fluid]]
-[[Category: disease mutation]]
-[[Category: liver]]
-[[Category: plasma]]
-[[Category: polymorphism]]
-[[Category: polyneuropathy]]
-[[Category: prealbumin]]
-[[Category: retinol-binding]]
-[[Category: signal]]
-[[Category: thyroid hormone]]
-[[Category: thyroxine]]
-[[Category: transport]]
-[[Category: vitamin a]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:38:01 2007''