5kr7: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Unreleased structure'''
-The entry 5kr7 is ON HOLD
+==KDM4C bound to pyrazolo-pyrimidine scaffold==
+<StructureSection load='5kr7' size='340' side='right'caption='[[5kr7]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5kr7]] 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=5KR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KR7 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]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6X9:6-ETHYL-2,5-DIMETHYL-7-OXIDANYLIDENE-4~{H}-PYRAZOLO[1,5-A]PYRIMIDINE-3-CARBONITRILE'>6X9</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</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=5kr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kr7 OCA], [https://pdbe.org/5kr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kr7 RCSB], [https://www.ebi.ac.uk/pdbsum/5kr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kr7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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 ==
+This communication describes the identification and optimization of a series of pan-KDM5 inhibitors derived from compound 1, a hit initially identified against KDM4C. Compound 1 was optimized to afford compound 20, a 10nM inhibitor of KDM5A. Compound 20 is highly selective for the KDM5 enzymes versus other histone lysine demethylases and demonstrates activity in a cellular assay measuring the increase in global histone 3 lysine 4 tri-methylation (H3K4me3). In addition compound 20 has good ADME properties, excellent mouse PK, and is a suitable starting point for further optimization.
-Authors: Bellon, S.F., Poy, F., Setser, J.W.
+Identification of potent, selective KDM5 inhibitors.,Gehling VS, Bellon SF, Harmange JC, LeBlanc Y, Poy F, Odate S, Buker S, Lan F, Arora S, Williamson KE, Sandy P, Cummings RT, Bailey CM, Bergeron L, Mao W, Gustafson A, Liu Y, VanderPorten E, Audia JE, Trojer P, Albrecht BK Bioorg Med Chem Lett. 2016 Sep 1;26(17):4350-4. doi: 10.1016/j.bmcl.2016.07.026. , Epub 2016 Jul 19. PMID:27476424<ref>PMID:27476424</ref>
-Description: KDM4C bound to pyrazolo-pyrimidine scaffold
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Poy, F]]
+<div class="pdbe-citations 5kr7" style="background-color:#fffaf0;"></div>
-[[Category: Bellon, S.F]]
-[[Category: Setser, J.W]]
+==See Also==
+*[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bellon SF]]
+[[Category: Poy F]]
+[[Category: Setser JW]]