5f5a: Difference between revisions
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==Crystal Structure of human JMJD2D complexed with KDOAM16== | ==Crystal Structure of human JMJD2D complexed with KDOAM16== | ||
<StructureSection load='5f5a' size='340' side='right' caption='[[5f5a]], [[Resolution|resolution]] 1.41Å' scene=''> | <StructureSection load='5f5a' size='340' side='right'caption='[[5f5a]], [[Resolution|resolution]] 1.41Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5f5a]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F5A OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5f5a]] 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=5F5A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F5A FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5V0:2-[(FURAN-2-YLMETHYLAMINO)METHYL]PYRIDINE-4-CARBOXYLIC+ACID'>5V0</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.41Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5V0:2-[(FURAN-2-YLMETHYLAMINO)METHYL]PYRIDINE-4-CARBOXYLIC+ACID'>5V0</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5f5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f5a OCA], [https://pdbe.org/5f5a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f5a RCSB], [https://www.ebi.ac.uk/pdbsum/5f5a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f5a ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Jumonji domain-containing protein|Jumonji domain-containing protein]] | *[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Arrowsmith | [[Category: Homo sapiens]] | ||
[[Category: Bountra | [[Category: Large Structures]] | ||
[[Category: Bradley | [[Category: Arrowsmith CH]] | ||
[[Category: Brennan | [[Category: Bountra C]] | ||
[[Category: Burgess-Brown | [[Category: Bradley AR]] | ||
[[Category: Crawley | [[Category: Brennan P]] | ||
[[Category: Burgess-Brown N]] | |||
[[Category: Edwards | [[Category: Crawley L]] | ||
[[Category: Krojer | [[Category: Edwards A]] | ||
[[Category: Oppermann | [[Category: Krojer T]] | ||
[[Category: Ruda | [[Category: Oppermann U]] | ||
[[Category: Ruda GF]] | |||
[[Category: Szykowska | [[Category: Szykowska A]] | ||
[[Category: Vollmar | [[Category: Vollmar M]] | ||
[[Category: Yang | [[Category: Yang H]] | ||
[[Category: | [[Category: Von Delft F]] | ||
Latest revision as of 11:47, 12 July 2023
Crystal Structure of human JMJD2D complexed with KDOAM16Crystal Structure of human JMJD2D complexed with KDOAM16
Structural highlights
FunctionKDM4D_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 PubMedWe report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-methyl lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me3 and H3K4Me3 demethylation in a cell-based assay. 8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors.,Bavetsias V, Lanigan RM, Ruda GF, Atrash B, McLaughlin MG, Tumber A, Mok NY, Le Bihan YV, Dempster S, Boxall KJ, Jeganathan F, Hatch SB, Savitsky P, Velupillai S, Krojer T, England KS, Sejberg J, Thai C, Donovan A, Pal A, Scozzafava G, Bennett JM, Kawamura A, Johansson C, Szykowska A, Gileadi C, Burgess-Brown NA, von Delft F, Oppermann U, Walters Z, Shipley J, Raynaud FI, Westaway SM, Prinjha RK, Fedorov O, Burke R, Schofield CJ, Westwood IM, Bountra C, Muller S, van Montfort RL, Brennan PE, Blagg J J Med Chem. 2016 Jan 7. PMID:26741168[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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