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==Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease==
==Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease==
<StructureSection load='4cbt' size='340' side='right' caption='[[4cbt]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
<StructureSection load='4cbt' size='340' side='right'caption='[[4cbt]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4cbt]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CBT FirstGlance]. <br>
<table><tr><td colspan='2'>[[4cbt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CBT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9F4:(1R,2R,3R)-2-[4-(5-FLUORANYLPYRIMIDIN-2-YL)PHENYL]-N-OXIDANYL-3-PHENYL-CYCLOPROPANE-1-CARBOXAMIDE'>9F4</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]] 3.03&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cby|4cby]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9F4:(1R,2R,3R)-2-[4-(5-FLUORANYLPYRIMIDIN-2-YL)PHENYL]-N-OXIDANYL-3-PHENYL-CYCLOPROPANE-1-CARBOXAMIDE'>9F4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4cbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbt OCA], [https://pdbe.org/4cbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cbt RCSB], [https://www.ebi.ac.uk/pdbsum/4cbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbt 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=4cbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbt OCA], [http://pdbe.org/4cbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cbt RCSB], [http://www.ebi.ac.uk/pdbsum/4cbt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbt ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/HDAC4_HUMAN HDAC4_HUMAN]] Defects in HDAC4 are the cause of brachydactyly-mental retardation syndrome (BDMR) [MIM:[http://omim.org/entry/600430 600430]]. A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism.<ref>PMID:20691407</ref>
[https://www.uniprot.org/uniprot/HDAC4_HUMAN HDAC4_HUMAN] Defects in HDAC4 are the cause of brachydactyly-mental retardation syndrome (BDMR) [MIM:[https://omim.org/entry/600430 600430]. A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism.<ref>PMID:20691407</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/HDAC4_HUMAN HDAC4_HUMAN]] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D.<ref>PMID:10523670</ref>
[https://www.uniprot.org/uniprot/HDAC4_HUMAN HDAC4_HUMAN] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D.<ref>PMID:10523670</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 4cbt" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 4cbt" style="background-color:#fffaf0;"></div>
==See Also==
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Histone deacetylase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Aziz, O]]
[[Category: Aziz O]]
[[Category: Beaumont, V]]
[[Category: Beaumont V]]
[[Category: Beconi, M]]
[[Category: Beconi M]]
[[Category: Breccia, P]]
[[Category: Breccia P]]
[[Category: Burli, R W]]
[[Category: Burli RW]]
[[Category: Connell, C O]]
[[Category: Dominguez C]]
[[Category: Dominguez, C]]
[[Category: Haughan AF]]
[[Category: Haughan, A F]]
[[Category: Hughes S]]
[[Category: Hughes, S]]
[[Category: Jarvis R]]
[[Category: Jarvis, R]]
[[Category: Lamers M]]
[[Category: Lamers, M]]
[[Category: Leonard P]]
[[Category: Leonard, P]]
[[Category: Luckhurst CA]]
[[Category: Luckhurst, C A]]
[[Category: Lyons KA]]
[[Category: Lyons, K A]]
[[Category: Maillard M]]
[[Category: Maillard, M]]
[[Category: Mangette J]]
[[Category: Mangette, J]]
[[Category: Matthews KL]]
[[Category: Matthews, K L]]
[[Category: McAllister G]]
[[Category: McAllister, G]]
[[Category: McNeil H]]
[[Category: McNeil, H]]
[[Category: Mead T]]
[[Category: Mead, T]]
[[Category: Mueller I]]
[[Category: Mueller, I]]
[[Category: Munoz-Sanjuan I]]
[[Category: Munoz-Sanjuan, I]]
[[Category: O'Connell C]]
[[Category: Penrose, S D]]
[[Category: Penrose SD]]
[[Category: Richardson, C M]]
[[Category: Richardson CM]]
[[Category: Stones, L]]
[[Category: Stones L]]
[[Category: Stott, A J]]
[[Category: Stott AJ]]
[[Category: Vann, J]]
[[Category: Vann J]]
[[Category: Wall, M]]
[[Category: Wall M]]
[[Category: Wishart, G]]
[[Category: Wishart G]]
[[Category: Yates, D]]
[[Category: Yates D]]
[[Category: Amyotrophic lateral sclerosis]]
[[Category: Class iia histone deacetylase inhibitor]]
[[Category: Cyclopropanation]]
[[Category: Huntingtons disease]]
[[Category: Hydrolase]]
[[Category: Hydroxamic acid]]
[[Category: Muscle atrophy]]
[[Category: Neurodegeneration]]
[[Category: Sar]]