View source for 6ful


==Crystal structure of UTX complexed with 5-hydroxy-4-keto-1-methyl-picolinate==
<StructureSection load='6ful' size='340' side='right'caption='[[6ful]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ful]] is a 1 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=6FUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FUL 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]] 1.649&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E7Z:1-methyl-5-oxidanyl-4-oxidanylidene-pyridine-2-carboxylic+acid'>E7Z</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6ful FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ful OCA], [https://pdbe.org/6ful PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ful RCSB], [https://www.ebi.ac.uk/pdbsum/6ful PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ful ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KDM6A_HUMAN KDM6A_HUMAN] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/KDM6A_HUMAN KDM6A_HUMAN] Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A.<ref>PMID:17851529</ref> <ref>PMID:17761849</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In the search for new demethylase inhibitors, we have developed a multistep protocol for in silico screening. Millions of poses generated by high-throughput docking or a 3D-pharmacophore search are first minimized by a classical force field and then filtered by semiempirical quantum mechanical calculations of the interaction energy with a selected set of functional groups in the binding site. The final ranking includes solvation effects which are evaluated in the continuum dielectric approximation (finite-difference Poisson equation). Application of the multistep protocol to JMJD3 jumonji demethylase has resulted in a dozen low-micromolar inhibitors belonging to five different chemical classes. We have solved the crystal structure of JMJD3 inhibitor 8 in the complex with UTX (a demethylase in the same subfamily as JMJD3) which validates the predicted binding mode. Compound 8 is a promising candidate for future optimization as it has a favorable ligand efficiency of 0.32 kcal/mol per nonhydrogen atom.

In Silico Identification of JMJD3 Demethylase Inhibitors.,Esposito C, Wiedmer L, Caflisch A J Chem Inf Model. 2018 Oct 3. doi: 10.1021/acs.jcim.8b00539. PMID:30226987<ref>PMID:30226987</ref>

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

==See Also==
*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Caflisch A]]
[[Category: Esposito C]]
[[Category: Sledz P]]