4y9g

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
'''Unreleased structure'''
+
==Crystal structure of V30M mutated transthyretin in complex with 3-isomangostin==
 +
<StructureSection load='4y9g' size='340' side='right' caption='[[4y9g]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4y9g]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y9G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y9G FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MKU:5,9-DIHYDROXY-8-METHOXY-2,2-DIMETHYL-7-(3-METHYLBUT-2-EN-1-YL)-3,4-DIHYDRO-2H,6H-PYRANO[3,2-B]XANTHEN-6-ONE'>MKU</scene></td></tr>
 +
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pwe|4pwe]], [[4y9b|4y9b]], [[4y9c|4y9c]], [[4y9e|4y9e]], [[4y9f|4y9f]]</td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4y9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y9g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y9g RCSB], [http://www.ebi.ac.uk/pdbsum/4y9g PDBsum]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[[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>
 +
== Function ==
 +
[[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>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Transthyretin (TTR) is a homotetrameric protein involved in human hereditary amyloidoses. The discovery and development of small molecules that inhibit the amyloid fibril formation of TTR is one of the therapeutic strategies for these diseases. Herein, we discovered that gamma-mangostin (gamma-M) is an effective inhibitor against the amyloid fibril formation of V30M amyloidogenic TTR. In-vitro binding assays revealed that gamma-M was the most potent of the selected xanthone derivatives, and it bound to the thyroxine (T4)-binding sites and stabilized the TTR tetramer. X-ray crystallographic analysis revealed the diagonal binding mode of gamma-M and the two binding sites of chloride ions at the T4-binding site. One of the chloride ions was replaced with a water molecule in the alpha-mangostin complex, which is a methylated derivative of gamma-M. The stronger inhibitory potency of gamma-M could be explained by the additional hydrogen bonds with the chloride ion. The present study establishes gamma-M as a novel inhibitor of TTR fibrillization.
-
The entry 4y9g is ON HOLD until Paper Publication
+
Discovery of gamma-Mangostin as an Amyloidogenesis Inhibitor.,Yokoyama T, Ueda M, Ando Y, Mizuguchi M Sci Rep. 2015 Aug 27;5:13570. doi: 10.1038/srep13570. PMID:26310724<ref>PMID:26310724</ref>
-
Authors: Yokoyama, T., Mizuguchi, M.
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
Description:
+
== References ==
-
[[Category: Unreleased Structures]]
+
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Mizuguchi, M]]
[[Category: Yokoyama, T]]
[[Category: Yokoyama, T]]
-
[[Category: Mizuguchi, M]]
+
[[Category: Amyloidosis]]
 +
[[Category: Inhibitor]]
 +
[[Category: Kinetic stabilizer]]
 +
[[Category: Mangostin]]
 +
[[Category: Natural product]]
 +
[[Category: Transport protein-inhibitor complex]]
 +
[[Category: Transporter]]
 +
[[Category: Transthyretin]]

Revision as of 11:10, 9 September 2015

Crystal structure of V30M mutated transthyretin in complex with 3-isomangostin

4y9g, resolution 1.89Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4y9g"
Personal tools