6hu0 - Revision history

OCA at 11:39, 24 January 2024

OCA — Wed, 24 Jan 2024 11:39:35 GMT

←Older revision		Revision as of 11:39, 24 January 2024
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	==Crystal structure of Schistosoma mansoni HDAC8 complexed with a benzohydroxamate inhibitor 9==		==Crystal structure of Schistosoma mansoni HDAC8 complexed with a benzohydroxamate inhibitor 9==
-	<StructureSection load='6hu0' size='340' side='right' caption='[[6hu0]], [[Resolution\|resolution]] 1.75Å' scene=''>	+	<StructureSection load='6hu0' size='340' side='right'caption='[[6hu0]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hu0]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Blood_fluke Blood fluke~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HU0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6HU0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hu0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HU0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=T86:3-[(2,4-dichlorophenyl)carbonylamino]-4-methoxy-~{N}-oxidanyl-benzamide'>T86</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]] 1.746Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HDAC8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6183 Blood fluke])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=T86:3-[(2,4-dichlorophenyl)carbonylamino]-4-methoxy-~{N}-oxidanyl-benzamide'>T86</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </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=6hu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hu0 OCA], [https://pdbe.org/6hu0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hu0 RCSB], [https://www.ebi.ac.uk/pdbsum/6hu0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hu0 ProSAT]</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=6hu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hu0 OCA], [~~http~~://pdbe.org/6hu0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6hu0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6hu0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6hu0 ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A5H660_SCHMA A5H660_SCHMA]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6hu0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6hu0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone deacetylase 3D structures\|Histone deacetylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Blood fluke~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Histone deacetylase~~]]	+	[[Category: Schistosoma mansoni]]
-	[[Category: Marek, M]]	+	[[Category: Marek M]]
-	[[Category: Romier, C]]	+	[[Category: Romier C]]
-	[[Category: Shaik~~, T B]]~~	+	[[Category: Shaik TB]]
-	~~[[Category: Epigenetic]]~~	+
-	~~[[Category: Hdac8]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Pathogen]]~~	+
-	~~[[Category: Selective inhibitor~~]]	+

OCA at 12:53, 7 November 2018

OCA — Wed, 07 Nov 2018 12:53:11 GMT

←Older revision		Revision as of 12:53, 7 November 2018
Line 3:		Line 3:
	<StructureSection load='6hu0' size='340' side='right' caption='[[6hu0]], [[Resolution\|resolution]] 1.75Å' scene=''>		<StructureSection load='6hu0' size='340' side='right' caption='[[6hu0]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hu0]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HU0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HU0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hu0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HU0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HU0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=T86:3-[(2,4-dichlorophenyl)carbonylamino]-4-methoxy-~{N}-oxidanyl-benzamide'>T86</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"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=T86:3-[(2,4-dichlorophenyl)carbonylamino]-4-methoxy-~{N}-oxidanyl-benzamide'>T86</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">HDAC8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6183 Blood fluke])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </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_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </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=6hu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hu0 OCA], [http://pdbe.org/6hu0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hu0 RCSB], [http://www.ebi.ac.uk/pdbsum/6hu0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hu0 ProSAT]</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=6hu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hu0 OCA], [http://pdbe.org/6hu0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hu0 RCSB], [http://www.ebi.ac.uk/pdbsum/6hu0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hu0 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Metal-dependent histone deacetylases (HDACs) are key epigenetic regulators that represent promising therapeutic targets for the treatment of numerous human diseases. Yet, the currently FDA-approved HDAC inhibitors non-specifically target at least several of the eleven structurally similar but functionally different HDAC isozymes, which hampers their broad usage in clinical settings. Selective inhibitors targeting single HDAC isozymes are being developed, but precise understanding in molecular terms of their selectivity remains sparse. Here, we show that HDAC8-selective inhibitors adopt a L-shaped conformation required for their binding to a HDAC8-specific pocket formed by HDAC8 catalytic tyrosine and HDAC8 L1 and L6 loops. In other HDAC isozymes, a L1-L6 lock sterically prevents L-shaped inhibitor binding. Shielding of the HDAC8-specific pocket by protein engineering decreases potency of HDAC8-selective inhibitors and affects catalytic activity. Collectively, our results unravel key HDAC8 active site structural and functional determinants important for the design of next-generation chemical probes and epigenetic drugs.
		+
		+	Characterization of histone deacetylase 8 (HDAC8) selective inhibition reveals specific active site structural and functional determinants.,Marek M, Shaik TB, Heimburg T, Chakrabarti A, Lancelot J, Ramos Morales E, Da Veiga C, Kalinin DV, Melesina J, Robaa D, Schmidtkunz K, Suzuki T, Holl R, Ennifar E, Pierce R, Jung M, Sippl W, Romier C J Med Chem. 2018 Oct 22. doi: 10.1021/acs.jmedchem.8b01087. PMID:30347148<ref>PMID:30347148</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6hu0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Blood fluke]]
	[[Category: Histone deacetylase]]		[[Category: Histone deacetylase]]
	[[Category: Marek, M]]		[[Category: Marek, M]]

OCA at 06:59, 31 October 2018

OCA — Wed, 31 Oct 2018 06:59:28 GMT

←Older revision		Revision as of 06:59, 31 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6hu0 is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of Schistosoma mansoni HDAC8 complexed with a benzohydroxamate inhibitor 9==
-		+	<StructureSection load='6hu0' size='340' side='right' caption='[[6hu0]], [[Resolution\|resolution]] 1.75Å' scene=''>
-	~~Authors~~: ~~Shaik~~, T.B., ~~Marek~~, M., ~~Romier~~, C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6hu0]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HU0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HU0 FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of Schistosoma mansoni HDAC8 complexed with a benzohydroxamate inhibitor 9~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=T86:3-[(2,4-dichlorophenyl)carbonylamino]-4-methoxy-~{N}-oxidanyl-benzamide'>T86</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </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=6hu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hu0 OCA], [http://pdbe.org/6hu0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hu0 RCSB], [http://www.ebi.ac.uk/pdbsum/6hu0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hu0 ProSAT]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histone deacetylase]]
		+	[[Category: Marek, M]]
	[[Category: Romier, C]]		[[Category: Romier, C]]
-	[[Category: ~~Marek~~, M]]	+	[[Category: Shaik, T B]]
-	[[Category: ~~Shaik, T.B~~]]	+	[[Category: Epigenetic]]
		+	[[Category: Hdac8]]
		+	[[Category: Hydrolase]]
		+	[[Category: Pathogen]]
		+	[[Category: Selective inhibitor]]

OCA at 06:13, 17 October 2018

OCA — Wed, 17 Oct 2018 06:13:49 GMT

←Older revision		Revision as of 06:13, 17 October 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hu0 is ON HOLD	+	The entry 6hu0 is ON HOLD until Paper Publication

	Authors: Shaik, T.B., Marek, M., Romier, C.		Authors: Shaik, T.B., Marek, M., Romier, C.

OCA: Protected "6hu0" [edit=sysop:move=sysop]

OCA — Wed, 10 Oct 2018 06:18:14 GMT

Protected "6hu0" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:18, 10 October 2018

OCA: New page: '''Unreleased structure''' The entry 6hu0 is ON HOLD Authors: Shaik, T.B., Marek, M., Romier, C. Description: Crystal structure of Schistosoma mansoni HDAC8 complexed with a benzohydro...

OCA — Wed, 10 Oct 2018 06:18:12 GMT

New page: '''Unreleased structure''' The entry 6hu0 is ON HOLD Authors: Shaik, T.B., Marek, M., Romier, C. Description: Crystal structure of Schistosoma mansoni HDAC8 complexed with a benzohydro...

New page

'''Unreleased structure'''

The entry 6hu0 is ON HOLD

Authors: Shaik, T.B., Marek, M., Romier, C.

Description: Crystal structure of Schistosoma mansoni HDAC8 complexed with a benzohydroxamate inhibitor 9
[[Category: Unreleased Structures]]
[[Category: Romier, C]]
[[Category: Marek, M]]
[[Category: Shaik, T.B]]