OCA at 14:16, 18 October 2023

OCA — Wed, 18 Oct 2023 14:16:58 GMT

←Older revision		Revision as of 14:16, 18 October 2023
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	==Structure of full-length human lambda-6A light chain JTO in complex with hydantoin stabilizer==		==Structure of full-length human lambda-6A light chain JTO in complex with hydantoin stabilizer==
-	<StructureSection load='6w4y' size='340' side='right'caption='[[6w4y]]' scene=''>	+	<StructureSection load='6w4y' size='340' side='right'caption='[[6w4y]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W4Y OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6W4Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w4y]] 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=6W4Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W4Y FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6w4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w4y OCA], [~~http~~://pdbe.org/6w4y PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6w4y RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6w4y PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6w4y ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.91Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7ZW:2-[(4~{R})-4-(2-methylpropyl)-2,5-bis(oxidanylidene)imidazolidin-1-yl]-~{N}-[4-(trifluoromethyl)phenyl]ethanamide'>7ZW</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6w4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w4y OCA], [https://pdbe.org/6w4y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w4y RCSB], [https://www.ebi.ac.uk/pdbsum/6w4y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w4y ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Misfolding and aggregation of immunoglobulin light chains (LCs) leads to the degeneration of post-mitotic tissue in the disease immunoglobulin LC amyloidosis (AL). We previously reported the discovery of small molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which slow or stop the LC aggregation cascade at the outset. A predominant structural category of kinetic stabilizers emerging from the high-throughput screen are coumarins substituted at the 7-position, which bind at the interface between the two variable domains of the light chain dimer. Here, we report the binding mode of another, more polar, LC kinetic stabilizer chemotype, 3,5-substituted hydantoins. Computational docking, solution nuclear magnetic resonance experiments, and x-ray crystallography show that the aromatic substructure emerging from the hydantoin 3-position occupies the same LC binding site as the coumarin ring. Notably, the hydantoin ring extends beyond the binding site mapped out by the coumarin hits. The hydantoin ring makes hydrogen bonds with both LC monomers simultaneously. The alkyl substructure at the hydantoin 5-position partially occupies a novel binding pocket proximal to the pocket occupied by the coumarin substructure. Overall, the hydantoin structural data suggest that a larger area of the LC variable-domain-variable-domain dimer interface is amenable to small molecule binding than previously demonstrated, which should facilitate development of more potent full-length LC kinetic stabilizers.
		+
		+	Structural basis for the stabilization of amyloidogenic immunoglobulin light chains by hydantoins.,Yan NL, Santos-Martins D, Rennella E, Sanchez BB, Chen JS, Kay LE, Wilson IA, Morgan GJ, Forli S, Kelly JW Bioorg Med Chem Lett. 2020 Aug 15;30(16):127356. doi: 10.1016/j.bmcl.2020.127356., Epub 2020 Jun 16. PMID:32631553<ref>PMID:32631553</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6w4y" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kelly JW]]		[[Category: Kelly JW]]
	[[Category: Morgan GJ]]		[[Category: Morgan GJ]]
	[[Category: Yan NL]]		[[Category: Yan NL]]

OCA at 11:42, 22 July 2020

OCA — Wed, 22 Jul 2020 11:42:00 GMT

←Older revision		Revision as of 11:42, 22 July 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6w4y is ~~ON HOLD until Paper Publication~~	+	==Structure of full-length human lambda-6A light chain JTO in complex with hydantoin stabilizer==
-		+	<StructureSection load='6w4y' size='340' side='right'caption='[[6w4y]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W4Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W4Y FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w4y OCA], [http://pdbe.org/6w4y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w4y RCSB], [http://www.ebi.ac.uk/pdbsum/6w4y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w4y ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Kelly JW]]
		+	[[Category: Morgan GJ]]
		+	[[Category: Yan NL]]

OCA at 03:56, 13 May 2020

OCA — Wed, 13 May 2020 03:56:34 GMT

←Older revision		Revision as of 03:56, 13 May 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6w4y is ON HOLD	+	The entry 6w4y is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6w4y" [edit=sysop:move=sysop]

OCA — Wed, 18 Mar 2020 08:36:04 GMT

Protected "6w4y" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:36, 18 March 2020

OCA: New page: '''Unreleased structure''' The entry 6w4y is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Mar 2020 08:36:03 GMT

New page: '''Unreleased structure''' The entry 6w4y is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6w4y is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6w4y - Revision history

OCA at 14:16, 18 October 2023

OCA at 11:42, 22 July 2020

OCA at 03:56, 13 May 2020

OCA: Protected "6w4y" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6w4y is ON HOLD Authors: Description: Category: Unreleased Structures