5wgl - Revision history

OCA at 14:12, 4 October 2023

OCA — Wed, 04 Oct 2023 14:12:31 GMT

←Older revision		Revision as of 14:12, 4 October 2023
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	==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with ricolinostat (ACY-1215)==		==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with ricolinostat (ACY-1215)==
-	<StructureSection load='5wgl' size='340' side='right' caption='[[5wgl]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='5wgl' size='340' side='right'caption='[[5wgl]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wgl]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Brachidanio_rerio Brachidanio~~ rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WGL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wgl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WGL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AH4:2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide'>AH4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.7Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">hdac6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AH4:2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide'>AH4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5wgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgl OCA], [~~http~~://pdbe.org/5wgl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wgl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wgl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgl 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=5wgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgl OCA], [https://pdbe.org/5wgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wgl RCSB], [https://www.ebi.ac.uk/pdbsum/5wgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgl ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 17:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5wgl" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wgl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone deacetylase 3D structures\|Histone deacetylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Brachidanio~~ rerio]]	+	[[Category: Danio rerio]]
-	[[Category: ~~Christianson, D W~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Porter, N J~~]]	+	[[Category: Christianson DW]]
-	[[Category: ~~Histone deacetylase]]~~	+	[[Category: Porter NJ]]
-	~~[[Category: Hydrolase inhibitor]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 06:44, 20 December 2017

OCA — Wed, 20 Dec 2017 06:44:19 GMT

←Older revision		Revision as of 06:44, 20 December 2017
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	<StructureSection load='5wgl' size='340' side='right' caption='[[5wgl]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='5wgl' size='340' side='right' caption='[[5wgl]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wgl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WGL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wgl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WGL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AH4:2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide'>AH4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=AH4:2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide'>AH4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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">hdac6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=5wgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgl OCA], [http://pdbe.org/5wgl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wgl RCSB], [http://www.ebi.ac.uk/pdbsum/5wgl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgl 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=5wgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgl OCA], [http://pdbe.org/5wgl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wgl RCSB], [http://www.ebi.ac.uk/pdbsum/5wgl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgl ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Histone deacetylases (HDACs) regulate myriad cellular processes by catalyzing the hydrolysis of acetyl-l-lysine residues in histone and nonhistone proteins. The Zn(2+)-dependent class IIb enzyme HDAC6 regulates microtubule function by deacetylating alpha-tubulin, which suppresses microtubule dynamics and leads to cell cycle arrest and apoptosis. Accordingly, HDAC6 is a target for the development of selective inhibitors that might be useful in new therapeutic approaches for the treatment of cancer, neurodegenerative diseases, and other disorders. Here, we present high-resolution structures of catalytic domain 2 from Danio rerio HDAC6 (henceforth simply "HDAC6") complexed with compounds that selectively inhibit HDAC6 while maintaining nanomolar inhibitory potency: N-hydroxy-4-[(N(2-hydroxyethyl)-2-phenylacetamido)methyl)-benzamide)] (HPB), ACY-1215 (Ricolinostat), and ACY-1083. These structures reveal that an unusual monodentate Zn(2+) coordination mode is exploited by sterically bulky HDAC6-selective phenylhydroxamate inhibitors. We additionally report the ultrahigh-resolution structure of the HDAC6-trichostatin A complex, which reveals two Zn(2+)-binding conformers for the inhibitor: a major conformer (70%) with canonical bidentate hydroxamate-Zn(2+) coordination geometry and a minor conformer (30%) with monodentate hydroxamate-Zn(2+) coordination geometry, reflecting a free energy difference of only 0.5 kcal/mol. The minor conformer is not visible in lower resolution structure determinations. Structural comparisons of HDAC6-inhibitor complexes with class I HDACs suggest active site features that contribute to the isozyme selectivity observed in biochemical assays.
		+
		+	Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors.,Porter NJ, Mahendran A, Breslow R, Christianson DW Proc Natl Acad Sci U S A. 2017 Dec 4. pii: 1718823114. doi:, 10.1073/pnas.1718823114. PMID:29203661<ref>PMID:29203661</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5wgl" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Brachidanio rerio]]
	[[Category: Christianson, D W]]		[[Category: Christianson, D W]]
	[[Category: Porter, N J]]		[[Category: Porter, N J]]

OCA at 07:17, 6 December 2017

OCA — Wed, 06 Dec 2017 07:17:37 GMT

←Older revision		Revision as of 07:17, 6 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5wgl is ON HOLD until Paper Publication~~	+	==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with ricolinostat (ACY-1215)==
-		+	<StructureSection load='5wgl' size='340' side='right' caption='[[5wgl]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~Authors: Porter, N.J., Christianson, D.W.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5wgl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WGL FirstGlance]. <br>
-	~~Description:~~ Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with ricolinostat (ACY-1215)	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AH4:2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide'>AH4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=5wgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgl OCA], [http://pdbe.org/5wgl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wgl RCSB], [http://www.ebi.ac.uk/pdbsum/5wgl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgl ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Porter,~~ N.J]]	+	</table>
-	[[Category: Christianson, D.W]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Christianson, D W]]
		+	[[Category: Porter, N J]]
		+	[[Category: Histone deacetylase]]
		+	[[Category: Hydrolase inhibitor]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA: Protected "5wgl" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 14:48:36 GMT

Protected "5wgl" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:48, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wgl is ON HOLD until Paper Publication Authors: Porter, N.J., Christianson, D.W. Description: Crystal structure of Danio rerio histone deacetylase...

OCA — Wed, 27 Sep 2017 14:48:35 GMT

New page: '''Unreleased structure''' The entry 5wgl is ON HOLD until Paper Publication Authors: Porter, N.J., Christianson, D.W. Description: Crystal structure of Danio rerio histone deacetylase...

New page

'''Unreleased structure'''

The entry 5wgl is ON HOLD until Paper Publication

Authors: Porter, N.J., Christianson, D.W.

Description: Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with ricolinostat (ACY-1215)
[[Category: Unreleased Structures]]
[[Category: Porter, N.J]]
[[Category: Christianson, D.W]]