6ett
From Proteopedia
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==Crystal structure of KDM4D with tetrazole compound 4== | ==Crystal structure of KDM4D with tetrazole compound 4== | ||
| - | <StructureSection load='6ett' size='340' side='right' caption='[[6ett]], [[Resolution|resolution]] 1.26Å' scene=''> | + | <StructureSection load='6ett' size='340' side='right'caption='[[6ett]], [[Resolution|resolution]] 1.26Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6ett]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ETT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ETT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ett]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ETT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ETT FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BXH:ethyl+2-(2~{H}-1,2,3,4-tetrazol-5-yl)ethanoate'>BXH</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BXH:ethyl+2-(2~{H}-1,2,3,4-tetrazol-5-yl)ethanoate'>BXH</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KDM4D, JHDM3D, JMJD2D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6ett FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ett OCA], [http://pdbe.org/6ett PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ett RCSB], [http://www.ebi.ac.uk/pdbsum/6ett PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ett ProSAT]</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=6ett FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ett OCA], [http://pdbe.org/6ett PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ett RCSB], [http://www.ebi.ac.uk/pdbsum/6ett PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ett ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | [[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 == | ||
| + | Human histone demethylases are known to play an important role in the development of several tumor types. Consequently, they have emerged as important medical targets for the treatment of human cancer. Herein, structural studies on tetrazolylhydrazide inhibitors as a new scaffold for a certain class of histone demethylases, the JmjC proteins, are reported. A series of compounds are structurally described and their respective binding modes to the KDM4D protein, which serves as a high-resolution model to represent the KDM4 subfamily in crystallographic studies, are examined. Similar to previously reported inhibitors, the compounds described herein are competitors for the natural KDM4 cofactor, 2-oxoglutarate. The tetrazolylhydrazide scaffold fills an important gap in KDM4 inhibition and newly described, detailed interactions of inhibitor moieties pave the way to the development of compounds with high target-binding affinity and increased membrane permeability, at the same time. | ||
| + | |||
| + | Structure-Based Screening of Tetrazolylhydrazide Inhibitors versus KDM4 Histone Demethylases.,Malecki PH, Ruger N, Roatsch M, Krylova O, Link A, Jung M, Heinemann U, Weiss MS ChemMedChem. 2019 Nov 6;14(21):1828-1839. doi: 10.1002/cmdc.201900441. Epub 2019 , Oct 10. PMID:31475772<ref>PMID:31475772</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ett" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Heinemann, U]] | [[Category: Heinemann, U]] | ||
[[Category: Link, A]] | [[Category: Link, A]] | ||
Revision as of 07:50, 11 March 2020
Crystal structure of KDM4D with tetrazole compound 4
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