View source for 6wyq


==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 1 (CD1) K330L mutant complexed with 4-iodo-SAHA==
<StructureSection load='6wyq' size='340' side='right'caption='[[6wyq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wyq]] is a 2 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=6WYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9000146&#8491;</td></tr>
<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=UFJ:N~1~-hydroxy-N~8~-(4-iodophenyl)octanediamide'>UFJ</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=6wyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyq OCA], [https://pdbe.org/6wyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyq RCSB], [https://www.ebi.ac.uk/pdbsum/6wyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The zinc hydrolase histone deacetylase 6 (HDAC6) is unique among vertebrate deacetylases in that it contains two catalytic domains, designated CD1 and CD2. Both domains are fully functional as lysine deacetylases in vitro. However, the in vivo function of only the CD2 domain is well defined, whereas that of the CD1 domain is more enigmatic. Three X-ray crystal structures of HDAC6 CD1-inhibitor complexes are now reported to broaden the understanding of affinity determinants in the active site. Notably, cocrystallization with inhibitors was facilitated by using active-site mutants of zebrafish HDAC6 CD1. The first mutant studied, H82F/F202Y HDAC6 CD1, was designed to mimic the active site of human HDAC6 CD1. The structure of its complex with trichostatin A was generally identical to that with the wild-type zebrafish enzyme. The second mutant studied, K330L HDAC6 CD1, was prepared to mimic the active site of HDAC6 CD2. It has previously been demonstrated that this substitution does not perturb inhibitor binding conformations in HDAC6 CD1; here, this mutant facilitated cocrystallization with derivatives of the cancer chemotherapy drug suberoylanilide hydroxamic acid (SAHA). These crystal structures allow the mapping of inhibitor-binding regions in the outer active-site cleft, where one HDAC isozyme typically differs from another. It is expected that these structures will help to guide the structure-based design of inhibitors with selectivity against HDAC6 CD1, which in turn will enable new chemical biology approaches to probe its cellular function.

Binding of inhibitors to active-site mutants of CD1, the enigmatic catalytic domain of histone deacetylase 6.,Osko JD, Christianson DW Acta Crystallogr F Struct Biol Commun. 2020 Sep 1;76(Pt 9):428-437. doi:, 10.1107/S2053230X20010250. Epub 2020 Aug 19. PMID:32880591<ref>PMID:32880591</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wyq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
*[[TRNA methyltransferase 3D structures|TRNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Christianson DW]]
[[Category: Osko JD]]