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==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (Y745F mutant) in complex with alpha tubulin K40 tripeptide substrate== | ==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (Y745F mutant) in complex with alpha tubulin K40 tripeptide substrate== | ||
<StructureSection load='5efk' size='340' side='right' caption='[[5efk]], [[Resolution|resolution]] 1.82Å' scene=''> | <StructureSection load='5efk' size='340' side='right'caption='[[5efk]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5efk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EFK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EFK FirstGlance]. <br> | <table><tr><td colspan='2'>[[5efk]] 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=5EFK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EFK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MCM:7-AMINO-4-METHYL-CHROMEN-2-ONE'>MCM</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MCM:7-AMINO-4-METHYL-CHROMEN-2-ONE'>MCM</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5edu|5edu]], [[5eef|5eef]], [[5eei|5eei]], [[5eek|5eek]], [[5eem|5eem]], [[5een|5een]], [[5ef7|5ef7]], [[5ef8|5ef8]], [[5efb|5efb]], [[5efg|5efg]], [[5efh|5efh]], [[5efj|5efj]], [[5efn|5efn]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5edu|5edu]], [[5eef|5eef]], [[5eei|5eei]], [[5eek|5eek]], [[5eem|5eem]], [[5een|5een]], [[5ef7|5ef7]], [[5ef8|5ef8]], [[5efb|5efb]], [[5efg|5efg]], [[5efh|5efh]], [[5efj|5efj]], [[5efn|5efn]]</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='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=5efk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efk OCA], [http://pdbe.org/5efk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efk RCSB], [http://www.ebi.ac.uk/pdbsum/5efk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5efk 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=5efk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efk OCA], [http://pdbe.org/5efk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efk RCSB], [http://www.ebi.ac.uk/pdbsum/5efk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5efk ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5efk" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5efk" 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: Histone deacetylase]] | [[Category: Histone deacetylase]] | ||
[[Category: Large Structures]] | |||
[[Category: Christianson, D W]] | [[Category: Christianson, D W]] | ||
[[Category: Hai, Y]] | [[Category: Hai, Y]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 14:32, 25 December 2019
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (Y745F mutant) in complex with alpha tubulin K40 tripeptide substrateCrystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (Y745F mutant) in complex with alpha tubulin K40 tripeptide substrate
Structural highlights
Publication Abstract from PubMedHistone deacetylase 6 (HDAC6) is a critical target for drug design because of its role in oncogenic transformation and cancer metastasis, and is unique among all histone deacetylases in that it contains tandem catalytic domains designated CD1 and CD2. We now report the crystal structures of CD2 from Homo sapiens HDAC6 and of CD1 and CD2 from Danio rerio HDAC6. We correlated these structures with activity measurements using 13 different substrates. The catalytic activity of CD2 from both species exhibited broad substrate specificity, whereas that of CD1 was highly specific for substrates bearing C-terminal acetyllysine residues. Crystal structures of substrate complexes yielded unprecedented snapshots of the catalytic mechanism. Additionally, crystal structures of complexes with eight different inhibitors, including belinostat and panobinostat (currently used in cancer chemotherapy), the macrocyclic tetrapeptide HC toxin, and the HDAC6-specific inhibitor N-hydroxy-4-(2-((2-hydroxyethyl)(phenyl)amino)-2-oxoethyl)benzamide, revealed surprising new insight regarding changes in Zn2+ coordination and isozyme-specific inhibition. Histone deacetylase 6 structure and molecular basis of catalysis and inhibition.,Hai Y, Christianson DW Nat Chem Biol. 2016 Jul 25. doi: 10.1038/nchembio.2134. PMID:27454933[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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