6l5z - Revision history

OCA at 10:29, 15 November 2023

OCA — Wed, 15 Nov 2023 10:29:08 GMT

←Older revision		Revision as of 10:29, 15 November 2023
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-	====	+	==Crystal strucutre of AF9 YEATS domain in complex with a cyclopeptide inhibitor==
-	<StructureSection load='6l5z' size='340' side='right'caption='[[6l5z]]' scene=''>	+	<StructureSection load='6l5z' size='340' side='right'caption='[[6l5z]], [[Resolution\|resolution]] 3.05Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6l5z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L5Z 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=6l5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l5z OCA], [https://pdbe.org/6l5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l5z RCSB], [https://www.ebi.ac.uk/pdbsum/6l5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l5z 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]] 3.05Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALO:ALLO-THREONINE'>ALO</scene>, <scene name='pdbligand=EDX:(2~{S})-6-carbamimidamido-2-(phenylmethoxycarbonylamino)hexanoic+acid'>EDX</scene>, <scene name='pdbligand=EE0:(2~{R})-2-azanylpentanoic+acid'>EE0</scene>, <scene name='pdbligand=EE3:(2~{S})-2-azanyl-6-(1,3-oxazol-5-ylcarbonylamino)hexanoic+acid'>EE3</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6l5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l5z OCA], [https://pdbe.org/6l5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l5z RCSB], [https://www.ebi.ac.uk/pdbsum/6l5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l5z ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/AF9_HUMAN AF9_HUMAN] A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/AF9_HUMAN AF9_HUMAN] Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.<ref>PMID:20159561</ref> <ref>PMID:20471948</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	YEATS domains are newly identified epigenetic "readers" of histone lysine acetylation (Kac) and crotonylation (Kcr). The malfunction of YEATS-Kac/Kcr interactions has been found to be involved in the pathogenesis of human diseases, such as cancer. These discoveries suggest that the YEATS domains are promising novel drug targets. We and others recently reported the development of YEATS domain inhibitors. Although these inhibitors have a general preference toward the AF9 and ENL YEATS domains, selective inhibitors targeting either YEATS domain are challenging to develop as these two proteins share a high structural similarity. In this study, we identified a proximal site outside the acyllysine-binding pocket that can differentiate AF9 YEATS from ENL YEATS. Combinatorial targeting of both the acyllysine pocket and this additional site by conformationally preorganized cyclopeptides enabled the selective inhibition of the AF9 YEATS domain. The most selective inhibitor, JYX-3, showed a 38-fold higher binding affinity toward AF9 YEATS over ENL YEATS. Further investigations indicated that JYX-3 could engage with AF9 in living cells, disrupt the YEATS-dependent chromatin recruitment of AF9, and suppress the transcription of AF9 target genes.
		+
		+	Selective Targeting of AF9 YEATS Domain by Cyclopeptide Inhibitors with Preorganized Conformation.,Jiang Y, Chen G, Li XM, Liu S, Tian G, Li Y, Li X, Li H, Li XD J Am Chem Soc. 2020 Dec 23;142(51):21450-21459. doi: 10.1021/jacs.0c10324. Epub , 2020 Dec 11. PMID:33306911<ref>PMID:33306911</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6l5z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Synthetic construct]]
		+	[[Category: Chen G]]
		+	[[Category: Li H]]
		+	[[Category: Li Y]]

OCA at 08:56, 5 May 2021

OCA — Wed, 05 May 2021 08:56:48 GMT

←Older revision		Revision as of 08:56, 5 May 2021
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	<StructureSection load='6l5z' size='340' side='right'caption='[[6l5z]]' scene=''>		<StructureSection load='6l5z' size='340' side='right'caption='[[6l5z]]' 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= OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= 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=6l5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l5z OCA], [~~http~~://pdbe.org/6l5z PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6l5z RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6l5z PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6l5z ProSAT]</span></td></tr>	+	</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=6l5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l5z OCA], [https://pdbe.org/6l5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l5z RCSB], [https://www.ebi.ac.uk/pdbsum/6l5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l5z ProSAT]</span></td></tr>
	</table>		</table>
	__TOC__		__TOC__

OCA at 20:31, 28 October 2020

OCA — Wed, 28 Oct 2020 20:31:09 GMT

←Older revision		Revision as of 20:31, 28 October 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6l5z ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6l5z' size='340' side='right'caption='[[6l5z]]' scene=''>
-	~~Authors~~: ~~Li, Y~~.~~, Chen, G~~.~~, Li, H~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Crystal strucutre of AF9 YEATS domain in complex with~~ a ~~cyclopeptide inhibitor~~	+	</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=6l5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l5z OCA], [http://pdbe.org/6l5z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l5z RCSB], [http://www.ebi.ac.uk/pdbsum/6l5z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l5z ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: Li, H]]	+	__TOC__
-	[[Category: ~~Chen, G~~]]	+	</StructureSection>
-	[[Category: ~~Li, Y~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 07:19, 1 April 2020

OCA — Wed, 01 Apr 2020 07:19:21 GMT

←Older revision		Revision as of 07:19, 1 April 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6l5z is ON HOLD	+	The entry 6l5z is ON HOLD until Paper Publication

	Authors: Li, Y., Chen, G., Li, H.		Authors: Li, Y., Chen, G., Li, H.

OCA: Protected "6l5z" [edit=sysop:move=sysop]

OCA — Wed, 30 Oct 2019 07:22:40 GMT

Protected "6l5z" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:22, 30 October 2019

OCA: New page: '''Unreleased structure''' The entry 6l5z is ON HOLD Authors: Li, Y., Chen, G., Li, H. Description: Crystal strucutre of AF9 YEATS domain in complex with a cyclopeptide inhibitor [[Cat...

OCA — Wed, 30 Oct 2019 07:22:39 GMT

New page: '''Unreleased structure''' The entry 6l5z is ON HOLD Authors: Li, Y., Chen, G., Li, H. Description: Crystal strucutre of AF9 YEATS domain in complex with a cyclopeptide inhibitor [[Cat...

New page

'''Unreleased structure'''

The entry 6l5z is ON HOLD

Authors: Li, Y., Chen, G., Li, H.

Description: Crystal strucutre of AF9 YEATS domain in complex with a cyclopeptide inhibitor
[[Category: Unreleased Structures]]
[[Category: Li, H]]
[[Category: Chen, G]]
[[Category: Li, Y]]