5a3n: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 5a3n is ON HOLD
+==Crystal structure of human PLU-1 (JARID1B) in complex with KDOAM25a==
+<StructureSection load='5a3n' size='340' side='right'caption='[[5a3n]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5a3n]] 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=5A3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A3N 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]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=LQT:2-[[[2-[2-(DIMETHYLAMINO)ETHYL-ETHYL-AMINO]-2-OXIDANYLIDENE-ETHYL]AMINO]METHYL]PYRIDINE-4-CARBOXAMIDE'>LQT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5a3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a3n OCA], [https://pdbe.org/5a3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a3n RCSB], [https://www.ebi.ac.uk/pdbsum/5a3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a3n ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KDM5B_HUMAN KDM5B_HUMAN] Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5. In contrast, may act as a tumor suppressor for melanoma.<ref>PMID:12657635</ref> <ref>PMID:16645588</ref> <ref>PMID:17320161</ref> <ref>PMID:17363312</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe2+-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of &lt;100 nM for KDM5A-D in vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of approximately 50 muM and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation.
-Authors: Srikannathasan, V., Johansson, C., Gileadi, C., Nuzzi, A., Ruda, G.F., Kopec, J., von Delft, F., Arrowsmith, C.H., Bountra, C., Edwards, A., Brennan, P., Oppermann, U.
+Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells.,Tumber A, Nuzzi A, Hookway ES, Hatch SB, Velupillai S, Johansson C, Kawamura A, Savitsky P, Yapp C, Szykowska A, Wu N, Bountra C, Strain-Damerell C, Burgess-Brown NA, Ruda GF, Fedorov O, Munro S, England KS, Nowak RP, Schofield CJ, La Thangue NB, Pawlyn C, Davies F, Morgan G, Athanasou N, Muller S, Oppermann U, Brennan PE Cell Chem Biol. 2017 Mar 16;24(3):371-380. doi: 10.1016/j.chembiol.2017.02.006., Epub 2017 Mar 2. PMID:28262558<ref>PMID:28262558</ref>
-Description: Crystal structure of human PLU-1 (JARID1B) in complex with KDOAM25a
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Ruda, G.F]]
+<div class="pdbe-citations 5a3n" style="background-color:#fffaf0;"></div>
-[[Category: Bountra, C]]
-[[Category: Arrowsmith, C.H]]
+==See Also==
-[[Category: Gileadi, C]]
+*[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]]
-[[Category: Oppermann, U]]
+*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
-[[Category: Kopec, J]]
+== References ==
-[[Category: Von Delft, F]]
+<references/>
-[[Category: Johansson, C]]
+__TOC__
-[[Category: Edwards, A]]
+</StructureSection>
-[[Category: Brennan, P]]
+[[Category: Homo sapiens]]
-[[Category: Srikannathasan, V]]
+[[Category: Large Structures]]
-[[Category: Nuzzi, A]]
+[[Category: Arrowsmith CH]]
+[[Category: Bountra C]]
+[[Category: Brennan P]]
+[[Category: Edwards A]]
+[[Category: Gileadi C]]
+[[Category: Johansson C]]
+[[Category: Kopec J]]
+[[Category: Nuzzi A]]
+[[Category: Oppermann U]]
+[[Category: Ruda GF]]
+[[Category: Srikannathasan V]]
+[[Category: Von Delft F]]