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==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with HC toxin== | ==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with HC toxin== | ||
<StructureSection load='5efj' size='340' side='right' caption='[[5efj]], [[Resolution|resolution]] 1.73Å' scene=''> | <StructureSection load='5efj' size='340' side='right'caption='[[5efj]], [[Resolution|resolution]] 1.73Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5efj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[5efj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bipolaris_zeicola Bipolaris zeicola] and [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EFJ 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=NO3:NITRATE+ION'>NO3</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=NO3:NITRATE+ION'>NO3</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=5OM:(2S)-2-AMINO-8,8-DIHYDROXY-8-[(2S)-OXIRAN-2-YL]OCTANOIC+ACID'>5OM</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OM:(2S)-2-AMINO-8,8-DIHYDROXY-8-[(2S)-OXIRAN-2-YL]OCTANOIC+ACID'>5OM</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</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]], [[5efk|5efk]], [[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]], [[5efk|5efk]], [[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=5efj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efj OCA], [http://pdbe.org/5efj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efj RCSB], [http://www.ebi.ac.uk/pdbsum/5efj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5efj 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=5efj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efj OCA], [http://pdbe.org/5efj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efj RCSB], [http://www.ebi.ac.uk/pdbsum/5efj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5efj ProSAT]</span></td></tr> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Bipolaris zeicola]] | [[Category: Bipolaris zeicola]] | ||
[[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-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 14:32, 25 December 2019
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with HC toxinCrystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with HC toxin
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. References
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