6pdb - Revision history

OCA at 07:27, 11 October 2023

OCA — Wed, 11 Oct 2023 07:27:23 GMT

←Older revision		Revision as of 07:27, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6pdb' size='340' side='right'caption='[[6pdb]], [[Resolution\|resolution]] 2.42Å' scene=''>		<StructureSection load='6pdb' size='340' side='right'caption='[[6pdb]], [[Resolution\|resolution]] 2.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pdb]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PDB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6PDB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pdb]] is a 1 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=6PDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PDB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O9M:2-fluoro-3-methyl-N-(phenylsulfonyl)-5-(pyrimidin-2-yl)benzohydrazide'>O9M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.42Å</td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O9M:2-fluoro-3-methyl-N-(phenylsulfonyl)-5-(pyrimidin-2-yl)benzohydrazide'>O9M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KAT8, MOF, MYST1, PP7073 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6pdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pdb OCA], [https://pdbe.org/6pdb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pdb RCSB], [https://www.ebi.ac.uk/pdbsum/6pdb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pdb ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6pdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pdb OCA], [~~http~~://pdbe.org/6pdb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pdb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pdb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pdb ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KAT8_HUMAN KAT8_HUMAN]] Histone acetyltransferase which may be involved in transcriptional activation. May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex.<ref>PMID:12397079</ref> <ref>PMID:15923642</ref> <ref>PMID:20018852</ref>	+	[https://www.uniprot.org/uniprot/KAT8_HUMAN KAT8_HUMAN] Histone acetyltransferase which may be involved in transcriptional activation. May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex.<ref>PMID:12397079</ref> <ref>PMID:15923642</ref> <ref>PMID:20018852</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6pdb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6pdb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone acetyltransferase 3D structures\|Histone acetyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Histone acetyltransferase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Baell~~, J B~~]]	+	[[Category: Baell JB]]
-	[[Category: Hermans~~, S J~~]]	+	[[Category: Hermans SJ]]
-	[[Category: Parker~~, M W~~]]	+	[[Category: Parker MW]]
-	[[Category: Thomas, T]]	+	[[Category: Thomas T]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Myst]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:19, 27 May 2020

OCA — Wed, 27 May 2020 07:19:33 GMT

←Older revision		Revision as of 07:19, 27 May 2020
Line 3:		Line 3:
	<StructureSection load='6pdb' size='340' side='right'caption='[[6pdb]], [[Resolution\|resolution]] 2.42Å' scene=''>		<StructureSection load='6pdb' size='340' side='right'caption='[[6pdb]], [[Resolution\|resolution]] 2.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pdb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PDB OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PDB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pdb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PDB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PDB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O9M:2-fluoro-3-methyl-N-(phenylsulfonyl)-5-(pyrimidin-2-yl)benzohydrazide'>O9M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O9M:2-fluoro-3-methyl-N-(phenylsulfonyl)-5-(pyrimidin-2-yl)benzohydrazide'>O9M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KAT8, MOF, MYST1, PP7073 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6pdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pdb OCA], [http://pdbe.org/6pdb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pdb RCSB], [http://www.ebi.ac.uk/pdbsum/6pdb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pdb ProSAT]</span></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=6pdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pdb OCA], [http://pdbe.org/6pdb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pdb RCSB], [http://www.ebi.ac.uk/pdbsum/6pdb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pdb ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 25:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Baell, J B]]		[[Category: Baell, J B]]

OCA at 09:15, 1 April 2020

OCA — Wed, 01 Apr 2020 09:15:35 GMT

←Older revision		Revision as of 09:15, 1 April 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6pdb is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of MYST acetyltransferase domain in complex with inhibitor 80==
		+	<StructureSection load='6pdb' size='340' side='right'caption='[[6pdb]], [[Resolution\|resolution]] 2.42Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6pdb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PDB FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O9M:2-fluoro-3-methyl-N-(phenylsulfonyl)-5-(pyrimidin-2-yl)benzohydrazide'>O9M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6pdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pdb OCA], [http://pdbe.org/6pdb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pdb RCSB], [http://www.ebi.ac.uk/pdbsum/6pdb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pdb ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KAT8_HUMAN KAT8_HUMAN]] Histone acetyltransferase which may be involved in transcriptional activation. May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex.<ref>PMID:12397079</ref> <ref>PMID:15923642</ref> <ref>PMID:20018852</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A high-throughput screen designed to discover new inhibitors of histone acetyltransferase KAT6A uncovered CTX-0124143 (1), a unique aryl acylsulfonohydrazide with an IC50 of 1.0 muM. Using this acylsulfonohydrazide as a template, we herein disclose the results of our extensive structure-activity relationship investigations, which resulted in the discovery of advanced compounds such as 55 and 80. These two compounds represent significant improvements on our recently reported prototypical lead WM-8014 (3) as they are not only equivalently potent as inhibitors of KAT6A but are less lipophilic and significantly more stable to microsomal degradation. Furthermore, during this process, we discovered a distinct structural subclass that contains key 2-fluorobenzenesulfonyl and phenylpyridine motifs, culminating in the discovery of WM-1119 (4). This compound is a highly potent KAT6A inhibitor (IC50 = 6.3 nM; KD = 0.002 muM), competes with Ac-CoA by binding to the Ac-CoA binding site, and has an oral bioavailability of 56% in rats.

-	~~Authors: Hermans~~, S.J., ~~Parker~~, M~~.W.~~, ~~Thomas~~, T., Baell, J.B.	+	Discovery of Acylsulfonohydrazide-Derived Inhibitors of the Lysine Acetyltransferase, KAT6A, as Potent Senescence-Inducing Anti-Cancer Agents.,Priebbenow DL, Leaver DJ, Nguyen N, Cleary B, Lagiakos HR, Sanchez J, Xue L, Huang F, Sun Y, Mujumdar P, Mudududdla R, Varghese S, Teguh S, Charman SA, White KL, Shackleford DM, Katneni K, Cuellar M, Strasser JM, Dahlin JL, Walters MA, Street IP, Monahan BJ, Jarman KE, Jousset Sabroux H, Falk H, Chung MC, Hermans SJ, Downer NL, Parker MW, Voss AK, Thomas T, Baell JB J Med Chem. 2020 Mar 19. doi: 10.1021/acs.jmedchem.9b02071. PMID:32118427<ref>PMID:32118427</ref>

-	~~Description: Crystal structure~~ of ~~MYST~~ acetyltransferase ~~domain in complex with inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6pdb" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histone acetyltransferase]]
		+	[[Category: Large Structures]]
		+	[[Category: Baell, J B]]
		+	[[Category: Hermans, S J]]
		+	[[Category: Parker, M W]]
	[[Category: Thomas, T]]		[[Category: Thomas, T]]
-	[[Category: ~~Parker, M.W~~]]	+	[[Category: Complex]]
-	[[Category: ~~Baell, J.B~~]]	+	[[Category: Inhibitor]]
-	[[Category: ~~Hermans, S.J~~]]	+	[[Category: Myst]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 04:12, 3 July 2019

OCA — Wed, 03 Jul 2019 04:12:37 GMT

←Older revision		Revision as of 04:12, 3 July 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Hermans, S.J., Parker, M.W., Thomas, T., Baell, J.B.		Authors: Hermans, S.J., Parker, M.W., Thomas, T., Baell, J.B.

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

OCA — Wed, 26 Jun 2019 05:19:06 GMT

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

←Older revision

Revision as of 05:19, 26 June 2019

OCA: New page: '''Unreleased structure''' The entry 6pdb is ON HOLD Authors: Hermans, S.J., Parker, M.W., Thomas, T., Baell, J.B. Description: Crystal structure of MYST acetyltransferase domain in co...

OCA — Wed, 26 Jun 2019 05:19:05 GMT

New page: '''Unreleased structure''' The entry 6pdb is ON HOLD Authors: Hermans, S.J., Parker, M.W., Thomas, T., Baell, J.B. Description: Crystal structure of MYST acetyltransferase domain in co...

New page

'''Unreleased structure'''

The entry 6pdb is ON HOLD

Authors: Hermans, S.J., Parker, M.W., Thomas, T., Baell, J.B.

Description: Crystal structure of MYST acetyltransferase domain in complex with inhibitor
[[Category: Unreleased Structures]]
[[Category: Thomas, T]]
[[Category: Parker, M.W]]
[[Category: Baell, J.B]]
[[Category: Hermans, S.J]]