6uhv: Difference between revisions
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<StructureSection load='6uhv' size='340' side='right'caption='[[6uhv]], [[Resolution|resolution]] 2.53Å' scene=''> | <StructureSection load='6uhv' size='340' side='right'caption='[[6uhv]], [[Resolution|resolution]] 2.53Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6uhv]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6uhv]] 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=6UHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UHV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=XS6:6-[(3-AMINOPROPYL)AMINO]-N-HYDROXYHEXANAMIDE'>XS6</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]] 2.53Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=XS6:6-[(3-AMINOPROPYL)AMINO]-N-HYDROXYHEXANAMIDE'>XS6</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=6uhv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uhv OCA], [https://pdbe.org/6uhv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uhv RCSB], [https://www.ebi.ac.uk/pdbsum/6uhv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uhv ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6uhv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6uhv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Danio rerio]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Christianson | [[Category: Christianson DW]] | ||
[[Category: Herbst-Gervasoni | [[Category: Herbst-Gervasoni CJ]] | ||
Latest revision as of 10:51, 11 October 2023
Crystal Structure of Danio rerio Histone Deacetylase 10 in Complex with 6-[(3-aminopropyl)amino]-N-hydroxyhexanamideCrystal Structure of Danio rerio Histone Deacetylase 10 in Complex with 6-[(3-aminopropyl)amino]-N-hydroxyhexanamide
Structural highlights
FunctionHDA10_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).[1] Publication Abstract from PubMedEukaryotic histone deacetylase 10 (HDAC10) is a Zn(2+)-dependent hydrolase that exhibits catalytic specificity for the hydrolysis of the polyamine N(8)-acetylspermidine. The recently determined crystal structure of HDAC10 from Danio rerio (zebrafish) reveals a narrow active site cleft and a negatively charged "gatekeeper" (E274) that favors the binding of the slender cationic substrate. Because HDAC10 expression is upregulated in advanced-stage neuroblastoma and induces autophagy, the selective inhibition of HDAC10 suppresses the autophagic response and renders cancer cells more susceptible to cytotoxic chemotherapeutic drugs. Here, we describe X-ray crystal structures of zebrafish HDAC10 complexed with eight different analogues of N(8)-acetylspermidine. These analogues contain different Zn(2+)-binding groups, such as hydroxamate, thiolate, and the tetrahedral gem-diolate resulting from the addition of a Zn(2+)-bound water molecule to a ketone carbonyl group. Notably, the chemistry that accompanies the binding of ketonic substrate analogues is identical to the chemistry involved in the first step of catalysis, i.e., nucleophilic attack of a Zn(2+)-bound water molecule at the scissile carbonyl group of N(8)-acetylspermidine. The most potent inhibitor studied contains a thiolate Zn(2+)-binding group. These structures reveal interesting geometric changes in the metal coordination polyhedron that accommodate inhibitor binding. Additional interactions in the active site highlight features contributing to substrate specificity. These interactions are likely to contribute to inhibitor binding selectivity and will inform the future design of compounds selective for HDAC10 inhibition. Binding of N(8)-Acetylspermidine Analogues to Histone Deacetylase 10 Reveals Molecular Strategies for Blocking Polyamine Deacetylation.,Herbst-Gervasoni CJ, Christianson DW Biochemistry. 2019 Dec 2. doi: 10.1021/acs.biochem.9b00906. PMID:31746596[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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