OCA at 15:32, 18 October 2023

2023-10-18T15:32:16Z

←Older revision		Revision as of 15:32, 18 October 2023
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	==Crystal Structure of Danio rerio Histone Deacetylase 10 H137A Mutant in Complex with N8-Acetylspermidine (Tetrahedral Intermediate)==		==Crystal Structure of Danio rerio Histone Deacetylase 10 H137A Mutant in Complex with N8-Acetylspermidine (Tetrahedral Intermediate)==
-	<StructureSection load='7kus' size='340' side='right'caption='[[7kus]]' scene=''>	+	<StructureSection load='7kus' size='340' side='right'caption='[[7kus]], [[Resolution\|resolution]] 2.00Å' 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=7KUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KUS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kus]] is a 1 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=7KUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KUS 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=7kus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kus OCA], [https://pdbe.org/7kus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kus RCSB], [https://www.ebi.ac.uk/pdbsum/7kus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kus 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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=X54:1-({4-[(3-aminopropyl)amino]butyl}amino)ethane-1,1-diol'>X54</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'>[https://proteopedia.org/fgij/fg.htm?mol=7kus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kus OCA], [https://pdbe.org/7kus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kus RCSB], [https://www.ebi.ac.uk/pdbsum/7kus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kus ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HDA10_DANRE HDA10_DANRE] Polyamine deacetylase (PDAC), which acts preferentially on N(8)-acetylspermidine, and also on acetylcadaverine and acetylputrescine (PubMed:28516954). Exhibits attenuated catalytic activity toward N(1),N(8)-diacetylspermidine and very low activity, if any, toward N(1)-acetylspermidine (PubMed:28516954). Has a very weak lysine deacetylase, if any (PubMed:28516954).<ref>PMID:28516954</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Histone deacetylase 10 (HDAC10) is a zinc-dependent polyamine deacetylase enriched in the cytosol of eukaryotic cells. The active site of HDAC10 contains catalytic residues conserved in other HDAC isozymes that function as lysine deacetylases: Y307 assists the zinc ion in polarizing the substrate carbonyl for nucleophilic attack, and the H136-H137 dyad serves general base-general acid functions. As an inducer of autophagy, HDAC10 is an attractive target for the design of selective inhibitors that may be useful in cancer chemotherapy. Because detailed structural information regarding the catalytic mechanism of HDAC10 may inform new approaches to inhibitor design, we now report X-ray crystal structures of HDAC10 in which reaction intermediates with substrates N(8)-acetylspermidine and N-acetylputrescine are trapped in the active site. The Y307F substitution prevents activation of the substrate carbonyl for nucleophilic attack by the zinc-bound water molecule, thereby enabling crystallographic isolation of intact enzyme-substrate complexes. The H137A substitution removes the catalytically obligatory general acid, thereby enabling crystallographic isolation of oxyanionic tetrahedral intermediates. Finally, the acetate complex with the wild-type enzyme represents a product complex after dissociation of the polyamine coproduct. Taken together, these structures provide snapshots of the reaction coordinate of acetylpolyamine hydrolysis and are consistent with a mechanism in which tandem histidine residues H136 and H137 serve as general base and general acid catalysts, respectively. The function of the histidine dyad in the HDAC10 mechanism appears to be similar to that in HDAC6, but not HDAC8 in which both functions are served by the second histidine of the tandem pair.
		+
		+	X-ray Crystallographic Snapshots of Substrate Binding in the Active Site of Histone Deacetylase 10.,Herbst-Gervasoni CJ, Christianson DW Biochemistry. 2021 Feb 2;60(4):303-313. doi: 10.1021/acs.biochem.0c00936. Epub, 2021 Jan 15. PMID:33449614<ref>PMID:33449614</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kus" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone deacetylase 3D structures\|Histone deacetylase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Danio rerio]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Christianson DW]]		[[Category: Christianson DW]]
	[[Category: Herbst-Gervasoni CJ]]		[[Category: Herbst-Gervasoni CJ]]

OCA at 11:12, 3 February 2021

2021-02-03T11:12:42Z

←Older revision		Revision as of 11:12, 3 February 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7kus ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure of Danio rerio Histone Deacetylase 10 H137A Mutant in Complex with N8-Acetylspermidine (Tetrahedral Intermediate)==
-		+	<StructureSection load='7kus' size='340' side='right'caption='[[7kus]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KUS FirstGlance]. <br>
-	~~Description~~:	+	</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=7kus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kus OCA], [https://pdbe.org/7kus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kus RCSB], [https://www.ebi.ac.uk/pdbsum/7kus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kus ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Christianson DW]]
		+	[[Category: Herbst-Gervasoni CJ]]

OCA at 05:46, 6 January 2021

2021-01-06T05:46:14Z

←Older revision		Revision as of 05:46, 6 January 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

2020-12-02T05:55:50Z

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

←Older revision

Revision as of 05:55, 2 December 2020

OCA: New page: '''Unreleased structure''' The entry 7kus is ON HOLD Authors: Description: Category: Unreleased Structures

2020-12-02T05:55:49Z

New page: '''Unreleased structure''' The entry 7kus is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7kus is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7kus - Revision history

OCA at 15:32, 18 October 2023

OCA at 11:12, 3 February 2021

OCA at 05:46, 6 January 2021

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

OCA: New page: '''Unreleased structure''' The entry 7kus is ON HOLD Authors: Description: Category: Unreleased Structures