OCA at 05:27, 15 May 2024

OCA — Wed, 15 May 2024 05:27:15 GMT

←Older revision		Revision as of 05:27, 15 May 2024
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-	'''Unreleased structure'''

-	The entry ~~8wgt~~ is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of V30M-TTR in complex with compound 7==
		+	<StructureSection load='8wgt' size='340' side='right'caption='[[8wgt]], [[Resolution\|resolution]] 1.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8wgt]] 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=8WGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WGT 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]] 1.696Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WGJ:[4,7-bis(chloranyl)-2-ethyl-1-benzofuran-3-yl]-[3,5-bis(iodanyl)-4-oxidanyl-phenyl]methanone'>WGJ</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=8wgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wgt OCA], [https://pdbe.org/8wgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wgt RCSB], [https://www.ebi.ac.uk/pdbsum/8wgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wgt 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Transthyretin amyloidosis is a fatal disorder caused by transthyretin amyloid aggregation. Stabilizing the native structure of transthyretin is an effective approach to inhibit amyloid aggregation. To develop kinetic stabilizers of transthyretin, it is crucial to explore compounds that selectively bind to transthyretin in plasma. Our recent findings demonstrated that the uricosuric agent benziodarone selectively binds to transthyretin in plasma. Here, we report the development of benziodarone analogues with enhanced potency for selective binding to transthyretin in plasma compared to benziodarone. These analogues featured substituents of chlorine, bromine, iodine, a methyl group, or a trifluoromethyl group, at the 4-position of the benzofuran ring. X-ray crystal structure analysis revealed that CH...O hydrogen bonds and a halogen bond are important for the binding of the compounds to the thyroxine-binding sites. The bioavailability of benziodarone analogues with 4-Br, 4-Cl, or 4-CH(3) was comparable to that of tafamidis, a current therapeutic agent for transthyretin amyloidosis.

-	~~Authors:~~ Yokoyama, T.	+	Development of Benziodarone Analogues with Enhanced Potency for Selective Binding to Transthyretin in Human Plasma.,Mizuguchi M, Nakagawa Y, Yokoyama T, Okada T, Fujii K, Takahashi K, Luan NNT, Nabeshima Y, Kanamitsu K, Nakagawa S, Yamakawa S, Ueda M, Ando Y, Toyooka N J Med Chem. 2024 Apr 26;67(9):6987-7005. doi: 10.1021/acs.jmedchem.3c02286. PMID:38670538<ref>PMID:38670538</ref>

-	~~Description: Crystal structure~~ of ~~V30M~~-~~TTR in complex with compound 7~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Yokoyama, T]]	+	<div class="pdbe-citations 8wgt" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Yokoyama T]]

OCA at 09:11, 29 November 2023

OCA — Wed, 29 Nov 2023 09:11:18 GMT

←Older revision		Revision as of 09:11, 29 November 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8wgt is ON HOLD	+	The entry 8wgt is ON HOLD until Paper Publication

	Authors: Yokoyama, T.		Authors: Yokoyama, T.

OCA at 06:02, 22 November 2023

OCA — Wed, 22 Nov 2023 06:02:42 GMT

←Older revision		Revision as of 06:02, 22 November 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8wgt is ON HOLD ~~until Paper Publication~~	+	The entry 8wgt is ON HOLD

	Authors: Yokoyama, T.		Authors: Yokoyama, T.

OCA at 05:47, 15 November 2023

OCA — Wed, 15 Nov 2023 05:47:09 GMT

←Older revision		Revision as of 05:47, 15 November 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8wgt is ON HOLD	+	The entry 8wgt is ON HOLD until Paper Publication

	Authors: Yokoyama, T.		Authors: Yokoyama, T.

OCA: Protected "8wgt" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2023 05:32:02 GMT

Protected "8wgt" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:32, 27 September 2023

OCA: New page: '''Unreleased structure''' The entry 8wgt is ON HOLD Authors: Yokoyama, T. Description: Crystal structure of V30M-TTR in complex with compound 7 Category: Unreleased Structures [[C...

OCA — Wed, 27 Sep 2023 05:32:01 GMT

New page: '''Unreleased structure''' The entry 8wgt is ON HOLD Authors: Yokoyama, T. Description: Crystal structure of V30M-TTR in complex with compound 7 Category: Unreleased Structures [[C...

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