6g5w - Revision history

OCA at 11:50, 1 February 2024

2024-02-01T11:50:57Z

←Older revision		Revision as of 11:50, 1 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6g5w]] 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=6G5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6G5W FirstGlance]. <br>		<table><tr><td colspan='2'>[[6g5w]] 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=6G5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6G5W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ENZ:(4~{R})-5-methyl-4-phenyl-2-pyridin-2-yl-pyrazolidin-3-one'>ENZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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]] 1.83Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ENZ:(4~{R})-5-methyl-4-phenyl-2-pyridin-2-yl-pyrazolidin-3-one'>ENZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=6g5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g5w OCA], [https://pdbe.org/6g5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6g5w RCSB], [https://www.ebi.ac.uk/pdbsum/6g5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6g5w 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=6g5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g5w OCA], [https://pdbe.org/6g5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6g5w RCSB], [https://www.ebi.ac.uk/pdbsum/6g5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6g5w ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:02, 21 December 2022

2022-12-21T10:02:33Z

←Older revision		Revision as of 10:02, 21 December 2022
Line 3:		Line 3:
	<StructureSection load='6g5w' size='340' side='right'caption='[[6g5w]], [[Resolution\|resolution]] 1.83Å' scene=''>		<StructureSection load='6g5w' size='340' side='right'caption='[[6g5w]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6g5w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G5W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6G5W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6g5w]] 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=6G5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6G5W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ENZ:(4~{R})-5-methyl-4-phenyl-2-pyridin-2-yl-pyrazolidin-3-one'>ENZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ENZ:(4~{R})-5-methyl-4-phenyl-2-pyridin-2-yl-pyrazolidin-3-one'>ENZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6g5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g5w OCA], [~~http~~://pdbe.org/6g5w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6g5w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6g5w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6g5w 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=6g5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g5w OCA], [https://pdbe.org/6g5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6g5w RCSB], [https://www.ebi.ac.uk/pdbsum/6g5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6g5w ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KDM4A_HUMAN KDM4A_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. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref> Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref>	+	[https://www.uniprot.org/uniprot/KDM4A_HUMAN KDM4A_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. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref> Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Jumonji domain-containing lysine demethylase (KDM) enzymes are encoded by genes of the KDM superfamily. Activities of the KDM4 subfamily promote aggressive phenotypes associated with prostate cancer (PCa). Previously, we discovered a benzimidazole pyrazole molecule that inhibited KDM4 isoforms with properties tractable for development. Here, we demonstrate that a benzyl-substituted variant of this inhibitor exhibits improved potency in biochemical assays, is cell-permeable, and kills PCa cells at low micromolar concentrations. By X-ray crystallography and kinetics-based assays, we demonstrate that the mechanism of inhibition is complex, proceeding via competition with the enzyme for binding of active-site Fe(2+) and by populating a distal site on the enzyme surface. Furthermore, we provide evidence that the inhibitor's cytostatic properties arise from direct intracellular inhibition of KDM4 enzymes. PCa cells treated with the inhibitor exhibit reduced expression of genes regulated by the androgen receptor, an outcome accompanied by epigenetic maintenance of a heterochromatic state.
		+
		+	Enhanced Properties of a Benzimidazole Benzylpyrazole Lysine Demethylase Inhibitor: Mechanism-of-Action, Binding Site Analysis, and Activity in Cellular Models of Prostate Cancer.,Carter DM, Specker E, Malecki PH, Przygodda J, Dudaniec K, Weiss MS, Heinemann U, Nazare M, Gohlke U J Med Chem. 2021 Oct 14;64(19):14266-14282. doi: 10.1021/acs.jmedchem.1c00693. , Epub 2021 Sep 23. PMID:34555281<ref>PMID:34555281</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6g5w" 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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Carter~~, D M~~]]	+	[[Category: Carter DM]]
-	[[Category: Gohlke, U]]	+	[[Category: Gohlke U]]
-	[[Category: Heinemann, U]]	+	[[Category: Heinemann U]]
-	[[Category: Malecki~~, P H~~]]	+	[[Category: Malecki PH]]
-	[[Category: Nazare, M]]	+	[[Category: Nazare M]]
-	[[Category: Specker, E]]	+	[[Category: Specker E]]
-	[[Category: Weiss~~, M S]]~~	+	[[Category: Weiss MS]]
-	~~[[Category: Cancer]]~~	+
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Epigenetic]]~~	+
-	~~[[Category: Inhibitor design]]~~	+
-	~~[[Category: Jmjd2a]]~~	+
-	~~[[Category: Kdm4a]]~~	+
-	~~[[Category: Ligand binding]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 07:17, 10 April 2019

2019-04-10T07:17:35Z

←Older revision		Revision as of 07:17, 10 April 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6g5w is ~~ON HOLD until Paper Publication~~	+	==Crystal Structure of KDM4A with compound YP-03-038==
-		+	<StructureSection load='6g5w' size='340' side='right'caption='[[6g5w]], [[Resolution\|resolution]] 1.83Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6g5w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G5W FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ENZ:(4~{R})-5-methyl-4-phenyl-2-pyridin-2-yl-pyrazolidin-3-one'>ENZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6g5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g5w OCA], [http://pdbe.org/6g5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g5w RCSB], [http://www.ebi.ac.uk/pdbsum/6g5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g5w ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KDM4A_HUMAN KDM4A_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. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref> Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Carter, D M]]
		+	[[Category: Gohlke, U]]
		+	[[Category: Heinemann, U]]
		+	[[Category: Malecki, P H]]
		+	[[Category: Nazare, M]]
		+	[[Category: Specker, E]]
		+	[[Category: Weiss, M S]]
		+	[[Category: Cancer]]
		+	[[Category: Drug design]]
		+	[[Category: Epigenetic]]
		+	[[Category: Inhibitor design]]
		+	[[Category: Jmjd2a]]
		+	[[Category: Kdm4a]]
		+	[[Category: Ligand binding]]
		+	[[Category: Oxidoreductase]]

OCA at 04:25, 18 April 2018

2018-04-18T04:25:04Z

←Older revision		Revision as of 04:25, 18 April 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6g5w is ON HOLD	+	The entry 6g5w is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6g5w" [edit=sysop:move=sysop]

2018-04-11T12:38:41Z

Protected "6g5w" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:38, 11 April 2018

OCA: New page: '''Unreleased structure''' The entry 6g5w is ON HOLD Authors: Description: Category: Unreleased Structures

2018-04-11T12:38:40Z

New page: '''Unreleased structure''' The entry 6g5w is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6g5w is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]