1ttc: Difference between revisions

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-[[Image:1ttc.gif|left|200px]]
- {{Structure
+==THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL30MET VARIANT TO 1.7 ANGSTROMS RESOLUTION==
-|PDB= 1ttc |SIZE=350|CAPTION= <scene name='initialview01'>1ttc</scene>, resolution 1.7&Aring;
+<StructureSection load='1ttc' size='340' side='right'caption='[[1ttc]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND=
+<table><tr><td colspan='2'>[[1ttc]] 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=1TTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TTC FirstGlance]. <br>
-|ACTIVITY=
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
-|GENE=
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ttc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ttc OCA], [https://pdbe.org/1ttc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ttc RCSB], [https://www.ebi.ac.uk/pdbsum/1ttc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ttc 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/tt/1ttc_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=1ttc ConSurf].
+<div style="clear:both"></div>
-'''THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL30MET VARIANT TO 1.7 ANGSTROMS RESOLUTION'''
+==See Also==
+*[[Transthyretin 3D structures|Transthyretin 3D structures]]
+== References ==
-==Overview==
+<references/>
-The x-ray crystal structures of normal human transthyretin (prealbumin) and the amyloidogenic Val-30-Met variant have been refined at 1.7-A resolution to R-values of 0.168 and 0.179, respectively, for 19,882 and 20,362 reflections (Fobs &gt; 2.0 sigma). Standard deviations for stereochemical parameters are 0.018 and 0.022 A for bond distances, 0.030 and 0.038 A for angle distances, and 0.035 and 0.070 A for planar 1-4 distances. The newly refined normal structure shows improvement over the original structure of Blake and Swan (Blake, C. C. F., and Swan, I. D. A. (1971) J. Mol. Biol. 61, 217-224) in stereochemistry and in the conformation of the loop regions. Residues Arg-103, Thr-123, Asn-124, and Pro-125 have now been resolved, and residues 1-9 and 126-127 have been modeled with the aid of simulated annealing refinement. The functional form of transthyretin is a tetramer, having a cylindrical cavity which will bind thyroxine and an exterior binding site for the complex of retinol with retinol-binding protein. The monomer is a beta barrel flattened to become more like a sandwich with residue 30 in the interior. The methionyl for valyl substitution forces the beta sheets of the monomer as much as 1 A apart, resulting in a distortion of the thyroxine-binding cavity, in agreement with the independent observations that the Met-30 variant has low affinity for thyroxine.
+__TOC__
+</StructureSection>
-==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==
-TTC is a [[Single protein]] structure of 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=1TTC OCA].
-==Reference==
-The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30--&gt;Met variant to 1.7-A resolution., Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen L, J Biol Chem. 1993 Feb 5;268(4):2416-24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8428915 8428915]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Braden, B C.]]
+[[Category: Braden BC]]
-[[Category: Hamilton, J A.]]
+[[Category: Hamilton JA]]
-[[Category: Steinrauf, L K.]]
+[[Category: Steinrauf LK]]
-[[Category: transport(thyroxine)]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:22:57 2008''