4xdp

From Proteopedia

(Difference between revisions)

Revision as of 12:09, 12 April 2017

Crystal structure of human KDM4C catalytic domain bound to tris

Structural highlights

4xdp is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	4xdo
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]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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. A High-Throughput Mass Spectrometry Assay Coupled with Redox Activity Testing Reduces Artifacts and False Positives in Lysine Demethylase Screening. J Biomol Screen. 2015 Mar 9. pii: 1087057115575689. PMID:25755264 doi:http://dx.doi.org/10.1177/1087057115575689

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xdp"

Categories: Boriack-Sjodin, P A | Swinger, K K | Lysine-specific demethylase 4c

@@ Line 1: / Line 1: @@
 ==Crystal structure of human KDM4C catalytic domain bound to tris==
 <StructureSection load='4xdp' size='340' side='right' caption='[[4xdp]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xdo|4xdo]]</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=4xdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xdp RCSB], [http://www.ebi.ac.uk/pdbsum/4xdp PDBsum]</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=4xdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdp OCA], [http://pdbe.org/4xdp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xdp RCSB], [http://www.ebi.ac.uk/pdbsum/4xdp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xdp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4xdp" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Lysine-specific histone demethylase|Lysine-specific histone demethylase]]
+*[[Jumonji domain-containing protein|Jumonji domain-containing protein]]
 == References ==
 <references/>

4xdp

From Proteopedia

Revision as of 12:09, 12 April 2017

Crystal structure of human KDM4C catalytic domain bound to tris

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox