5kr7: Difference between revisions

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<StructureSection load='5kr7' size='340' side='right'caption='[[5kr7]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='5kr7' size='340' side='right'caption='[[5kr7]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5kr7]] is a 2 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=5KR7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KR7 FirstGlance]. <br>
<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='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>
</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KDM4C, GASC1, JHDM3C, JMJD2C, KIAA0780 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://proteopedia.org/fgij/fg.htm?mol=5kr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kr7 OCA], [http://pdbe.org/5kr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kr7 RCSB], [http://www.ebi.ac.uk/pdbsum/5kr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kr7 ProSAT]</span></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>
</table>
== Function ==
== Function ==
[[http://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>
[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;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bellon, S F]]
[[Category: Bellon SF]]
[[Category: Poy, F]]
[[Category: Poy F]]
[[Category: Setser, J W]]
[[Category: Setser JW]]
[[Category: Histone]]
[[Category: Inhibitor]]
[[Category: Lysine demethylase]]
[[Category: Oxidoreductase]]

Latest revision as of 13:52, 27 September 2023

KDM4C bound to pyrazolo-pyrimidine scaffoldKDM4C bound to pyrazolo-pyrimidine scaffold

Structural highlights

5kr7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1]

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.

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[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6. PMID:16603238 doi:10.1016/j.cell.2006.03.028
  2. ↑ 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. Identification of potent, selective KDM5 inhibitors. 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 doi:http://dx.doi.org/10.1016/j.bmcl.2016.07.026

5kr7, resolution 1.90Å

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