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==Crystal structure of human KDM4C catalytic domain with OGA==
==Crystal structure of human KDM4C catalytic domain with OGA==
<StructureSection load='4xdo' size='340' side='right' caption='[[4xdo]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
<StructureSection load='4xdo' size='340' side='right'caption='[[4xdo]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4xdo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XDO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XDO FirstGlance]. <br>
<table><tr><td colspan='2'>[[4xdo]] is a 2 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=4XDO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XDO 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=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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]] 1.97&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xml|2xml]], [[4xdp|4xdp]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xdo RCSB], [http://www.ebi.ac.uk/pdbsum/4xdo PDBsum]</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=4xdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdo OCA], [https://pdbe.org/4xdo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xdo RCSB], [https://www.ebi.ac.uk/pdbsum/4xdo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xdo ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/KDM4C_HUMAN KDM4C_HUMAN]] Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.<ref>PMID:16603238</ref> 
[https://www.uniprot.org/uniprot/KDM4C_HUMAN KDM4C_HUMAN] Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.<ref>PMID:16603238</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Demethylation of histones by lysine demethylases (KDMs) plays a critical role in controlling gene transcription. Aberrant demethylation may play a causal role in diseases such as cancer. Despite the biological significance of these enzymes, there are limited assay technologies for study of KDMs and few quality chemical probes available to interrogate their biology. In this report, we demonstrate the utility of self-assembled monolayer desorption/ionization (SAMDI) mass spectrometry for the investigation of quantitative KDM enzyme kinetics and for high-throughput screening for KDM inhibitors. SAMDI can be performed in 384-well format and rapidly allows reaction components to be purified prior to injection into a mass spectrometer, without a throughput-limiting liquid chromatography step. We developed sensitive and robust assays for KDM1A (LSD1, AOF2) and KDM4C (JMJD2C, GASC1) and screened 13,824 compounds against each enzyme. Hits were rapidly triaged using a redox assay to identify compounds that interfered with the catalytic oxidation chemistry used by the KDMs for the demethylation reaction. We find that overall this high-throughput mass spectrometry platform coupled with the elimination of redox active compounds leads to a hit rate that is manageable for follow-up work.
 
A High-Throughput Mass Spectrometry Assay Coupled with Redox Activity Testing Reduces Artifacts and False Positives in Lysine Demethylase Screening.,Wigle TJ, Swinger KK, Campbell JE, Scholle MD, Sherrill J, Admirand EA, Boriack-Sjodin PA, Kuntz KW, Chesworth R, Moyer MP, Scott MP, Copeland RA J Biomol Screen. 2015 Mar 9. pii: 1087057115575689. PMID:25755264<ref>PMID:25755264</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Boriack-Sjodin, P A]]
[[Category: Homo sapiens]]
[[Category: Swinger, K K]]
[[Category: Large Structures]]
[[Category: Lysine-specific demethylase 4c]]
[[Category: Boriack-Sjodin PA]]
[[Category: Oxidoreductase]]
[[Category: Swinger KK]]

Latest revision as of 16:00, 1 March 2024

Crystal structure of human KDM4C catalytic domain with OGACrystal structure of human KDM4C catalytic domain with OGA

Structural highlights

4xdo is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.97Å
Ligands:, , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KDM4C_HUMAN Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.[1]

See Also

References

  1. ↑ Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6. PMID:16603238 doi:10.1016/j.cell.2006.03.028

4xdo, resolution 1.97Å

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