5fpa

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human KDM4D in complex with 3H,4H-pyrido-3,4-d- pyrimidin-4-one

Structural highlights

5fpa is a 1 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 1.96Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[2]

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

References

↑ 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
↑ 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. Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives. J Med Chem. 2016 Jan 15. PMID:26771107 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01537

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5fpa"

Categories: Homo sapiens | Large Structures | Chung C

@@ Line 3: / Line 3: @@
 <StructureSection load='5fpa' size='340' side='right'caption='[[5fpa]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5fpa]] 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=5FPA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FPA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5fpa]] 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=5FPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FPA FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=N5J:3H-PYRIDO[3,4-D]PYRIMIDIN-4-ONE'>N5J</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]] 1.96&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=N5J:3H-PYRIDO[3,4-D]PYRIMIDIN-4-ONE'>N5J</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]], [[5fp8|5fp8]], [[5fp9|5fp9]], [[5fpb|5fpb]]</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=5fpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fpa OCA], [https://pdbe.org/5fpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fpa RCSB], [https://www.ebi.ac.uk/pdbsum/5fpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fpa ProSAT]</span></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=5fpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fpa OCA], [http://pdbe.org/5fpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fpa RCSB], [http://www.ebi.ac.uk/pdbsum/5fpa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fpa ProSAT]</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>
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chung, C]]
+[[Category: Chung C]]
-[[Category: Inhibitor]]
-[[Category: Jmjd2d]]
-[[Category: Jumonji]]
-[[Category: Kdm4d]]
-[[Category: Lysine specific histone demethylase]]
-[[Category: Oxidoreducatse]]
-[[Category: Oxidoreductase]]

5fpa

From Proteopedia

Current revision

Crystal structure of human KDM4D in complex with 3H,4H-pyrido-3,4-d- pyrimidin-4-one

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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