5fp8: Difference between revisions
m Protected "5fp8" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==Crystal structure of human KDM4D in complex with 3-4-methylthiophen-2- ylmethylaminopyridine-4-carboxylic acid== | ||
<StructureSection load='5fp8' size='340' side='right' caption='[[5fp8]], [[Resolution|resolution]] 1.98Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5fp8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FP8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FP8 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AUY:3-[(4-METHYLTHIOPHEN-2-YL)METHYLAMINO]PYRIDINE-4-CARBOXYLIC+ACID'>AUY</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">[[5fp3|5fp3]], [[5fp4|5fp4]], [[5fp7|5fp7]], [[5fp9|5fp9]], [[5fpa|5fpa]], [[5fpb|5fpb]]</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=5fp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fp8 OCA], [http://pdbe.org/5fp8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fp8 RCSB], [http://www.ebi.ac.uk/pdbsum/5fp8 PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/KDM4D_HUMAN KDM4D_HUMAN]] Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Demethylates both di- and trimethylated H3 'Lys-9' residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.<ref>PMID:16603238</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Optimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 </= 100 nM, in KDM4 family biochemical (RFMS) assays with >/=50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 muM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM). | |||
Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives.,Westaway SM, Preston AG, Barker MD, Brown F, Brown JA, Campbell M, Chung CW, Diallo H, Douault C, Drewes G, Eagle R, Gordon L, Haslam C, Hayhow TG, Humphreys PG, Joberty G, Katso R, Kruidenier L, Leveridge M, Liddle J, Mosley J, Muelbaier M, Randle R, Rioja I, Rueger A, Seal GA, Sheppard RJ, Singh O, Taylor J, Thomas P, Thomson D, Wilson DM, Lee K, Prinjha RK J Med Chem. 2016 Jan 15. PMID:26771107<ref>PMID:26771107</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5fp8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Chung, C]] | [[Category: Chung, C]] | ||
[[Category: Inhibitor]] | |||
[[Category: Jmjd2d]] | |||
[[Category: Jumonji]] | |||
[[Category: Kdm4d]] | |||
[[Category: Lysine specific histone demethylase]] | |||
[[Category: Oxidoreductase]] | |||
Revision as of 05:23, 28 January 2016
Crystal structure of human KDM4D in complex with 3-4-methylthiophen-2- ylmethylaminopyridine-4-carboxylic acidCrystal structure of human KDM4D in complex with 3-4-methylthiophen-2- ylmethylaminopyridine-4-carboxylic acid
Structural highlights
Function[KDM4D_HUMAN] Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Demethylates both di- and trimethylated H3 'Lys-9' residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.[1] Publication Abstract from PubMedOptimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 </= 100 nM, in KDM4 family biochemical (RFMS) assays with >/=50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 muM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM). Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives.,Westaway SM, Preston AG, Barker MD, Brown F, Brown JA, Campbell M, Chung CW, Diallo H, Douault C, Drewes G, Eagle R, Gordon L, Haslam C, Hayhow TG, Humphreys PG, Joberty G, Katso R, Kruidenier L, Leveridge M, Liddle J, Mosley J, Muelbaier M, Randle R, Rioja I, Rueger A, Seal GA, Sheppard RJ, Singh O, Taylor J, Thomas P, Thomson D, Wilson DM, Lee K, Prinjha RK J Med Chem. 2016 Jan 15. PMID:26771107[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||