7lmp - Revision history

OCA at 15:54, 18 October 2023

OCA — Wed, 18 Oct 2023 15:54:01 GMT

←Older revision		Revision as of 15:54, 18 October 2023
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	<StructureSection load='7lmp' size='340' side='right'caption='[[7lmp]], [[Resolution\|resolution]] 2.29Å' scene=''>		<StructureSection load='7lmp' size='340' side='right'caption='[[7lmp]], [[Resolution\|resolution]] 2.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7lmp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LMP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lmp]] 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=7LMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LMP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NY6:3-[2-[7-(diethylamino)-4-methyl-2-oxidanylidene-chromen-3-yl]ethyl]-8-(1~{H}-imidazol-5-ylcarbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione'>NY6</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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]] 2.29Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NY6:3-[2-[7-(diethylamino)-4-methyl-2-oxidanylidene-chromen-3-yl]ethyl]-8-(1~{H}-imidazol-5-ylcarbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione'>NY6</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=7lmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lmp OCA], [https://pdbe.org/7lmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lmp RCSB], [https://www.ebi.ac.uk/pdbsum/7lmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lmp ProSAT]</span></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=7lmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lmp OCA], [https://pdbe.org/7lmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lmp RCSB], [https://www.ebi.ac.uk/pdbsum/7lmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lmp ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kelly~~, J W~~]]	+	[[Category: Kelly JW]]
-	[[Category: Wilson~~, I A~~]]	+	[[Category: Wilson IA]]
-	[[Category: Yan~~, N L]]~~	+	[[Category: Yan NL]]
-	~~[[Category: Amyloidosis]]~~	+
-	~~[[Category: Immune system~~]]	+

OCA at 09:29, 26 May 2021

OCA — Wed, 26 May 2021 09:29:59 GMT

←Older revision		Revision as of 09:29, 26 May 2021
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	==Structure of full-length human lambda-6A light chain JTO in complex with stabilizer 36 [3-(2-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)-8-(1H-imidazole-4-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione]==		==Structure of full-length human lambda-6A light chain JTO in complex with stabilizer 36 [3-(2-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)-8-(1H-imidazole-4-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione]==
-	<StructureSection load='7lmp' size='340' side='right'caption='[[7lmp]]' scene=''>	+	<StructureSection load='7lmp' size='340' side='right'caption='[[7lmp]], [[Resolution\|resolution]] 2.29Å' 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=7LMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LMP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lmp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LMP FirstGlance]. <br>
-	</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=7lmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lmp OCA], [https://pdbe.org/7lmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lmp RCSB], [https://www.ebi.ac.uk/pdbsum/7lmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lmp ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NY6:3-[2-[7-(diethylamino)-4-methyl-2-oxidanylidene-chromen-3-yl]ethyl]-8-(1~{H}-imidazol-5-ylcarbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione'>NY6</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=7lmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lmp OCA], [https://pdbe.org/7lmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lmp RCSB], [https://www.ebi.ac.uk/pdbsum/7lmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lmp ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In immunoglobulin light-chain (LC) amyloidosis, transient unfolding or unfolding and proteolysis enable aggregation of LC proteins, causing potentially fatal organ damage. A drug that kinetically stabilizes LCs could suppress aggregation; however, LC sequences are variable and have no natural ligands, hindering drug development efforts. We previously identified high-throughput screening hits that bind to a site at the interface between the two variable domains of the LC homodimer. We hypothesized that extending the stabilizers beyond this initially characterized binding site would improve affinity. Here, using protease sensitivity assays, we identified stabilizers that can be divided into four substructures. Some stabilizers exhibit nanomolar EC50 values, a 3000-fold enhancement over the screening hits. Crystal structures reveal a key pi-pi stacking interaction with a conserved tyrosine residue that was not utilized by the screening hits. These data provide a foundation for developing LC stabilizers with improved binding selectivity and enhanced physicochemical properties.
		+
		+	Discovery of Potent Coumarin-Based Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains Using Structure-Based Design.,Yan NL, Santos-Martins D, Nair R, Chu A, Wilson IA, Johnson KA, Forli S, Morgan GJ, Petrassi HM, Kelly JW J Med Chem. 2021 May 13;64(9):6273-6299. doi: 10.1021/acs.jmedchem.1c00339. Epub , 2021 May 3. PMID:33939422<ref>PMID:33939422</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lmp" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kelly JW]]	+	[[Category: Kelly, J W]]
-	[[Category: Wilson IA]]	+	[[Category: Wilson, I A]]
-	[[Category: Yan NL]]	+	[[Category: Yan, N L]]
		+	[[Category: Amyloidosis]]
		+	[[Category: Immune system]]

OCA at 10:10, 19 May 2021

OCA — Wed, 19 May 2021 10:10:26 GMT

←Older revision		Revision as of 10:10, 19 May 2021
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-	'''Unreleased structure'''

-	~~The entry 7lmp is ON HOLD until Paper Publication~~	+	==Structure of full-length human lambda-6A light chain JTO in complex with stabilizer 36 [3-(2-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)-8-(1H-imidazole-4-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione]==
-		+	<StructureSection load='7lmp' size='340' side='right'caption='[[7lmp]]' scene=''>
-	~~Authors: Yan, N.L., Wilson, I.A., Kelly, J.W.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LMP FirstGlance]. <br>
-	~~Description:~~ Structure of full-length human lambda-6A light chain JTO in complex with stabilizer 36 [3-(2-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)-8-(1H-imidazole-4-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione]	+	</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=7lmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lmp OCA], [https://pdbe.org/7lmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lmp RCSB], [https://www.ebi.ac.uk/pdbsum/7lmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lmp ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Yan~~, N.L]]	+	__TOC__
-	[[Category: Kelly~~, J.W~~]]	+	</StructureSection>
-	[[Category: Wilson~~, I.A~~]]	+	[[Category: Large Structures]]
		+	[[Category: Kelly JW]]
		+	[[Category: Wilson IA]]
		+	[[Category: Yan NL]]

OCA at 13:22, 3 March 2021

OCA — Wed, 03 Mar 2021 13:22:54 GMT

←Older revision		Revision as of 13:22, 3 March 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7lmp is ON HOLD	+	The entry 7lmp is ON HOLD until Paper Publication

	Authors: Yan, N.L., Wilson, I.A., Kelly, J.W.		Authors: Yan, N.L., Wilson, I.A., Kelly, J.W.
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	Description: Structure of full-length human lambda-6A light chain JTO in complex with stabilizer 36 [3-(2-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)-8-(1H-imidazole-4-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione]		Description: Structure of full-length human lambda-6A light chain JTO in complex with stabilizer 36 [3-(2-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)-8-(1H-imidazole-4-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione]
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Yan, N.L]]
	[[Category: Kelly, J.W]]		[[Category: Kelly, J.W]]
	[[Category: Wilson, I.A]]		[[Category: Wilson, I.A]]
-	[[Category: Yan, N.L]]

OCA: Protected "7lmp" [edit=sysop:move=sysop]

OCA — Wed, 17 Feb 2021 08:46:04 GMT

Protected "7lmp" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:46, 17 February 2021

OCA: New page: '''Unreleased structure''' The entry 7lmp is ON HOLD Authors: Yan, N.L., Wilson, I.A., Kelly, J.W. Description: Structure of full-length human lambda-6A light chain JTO in complex with...

OCA — Wed, 17 Feb 2021 08:46:02 GMT

New page: '''Unreleased structure''' The entry 7lmp is ON HOLD Authors: Yan, N.L., Wilson, I.A., Kelly, J.W. Description: Structure of full-length human lambda-6A light chain JTO in complex with...

New page

'''Unreleased structure'''

The entry 7lmp is ON HOLD

Authors: Yan, N.L., Wilson, I.A., Kelly, J.W.

Description: Structure of full-length human lambda-6A light chain JTO in complex with stabilizer 36 [3-(2-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl)ethyl)-8-(1H-imidazole-4-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione]
[[Category: Unreleased Structures]]
[[Category: Kelly, J.W]]
[[Category: Wilson, I.A]]
[[Category: Yan, N.L]]