6bh2 - Revision history

OCA at 14:40, 4 October 2023

2023-10-04T14:40:16Z

←Older revision		Revision as of 14:40, 4 October 2023
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	<StructureSection load='6bh2' size='340' side='right'caption='[[6bh2]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='6bh2' size='340' side='right'caption='[[6bh2]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bh2]] 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=6BH2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6BH2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bh2]] 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=6BH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BH2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90V:N-{(3R)-1-[3-(PROPAN-2-YL)-1H-PYRAZOLE-5-CARBONYL]PYRROLIDIN-3-YL}CYCLOPROPANECARBOXAMIDE'>90V</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 1.447Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDM5A, JARID1A, RBBP2, RBP2 ([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=90V:N-{(3R)-1-[3-(PROPAN-2-YL)-1H-PYRAZOLE-5-CARBONYL]PYRROLIDIN-3-YL}CYCLOPROPANECARBOXAMIDE'>90V</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=6bh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bh2 OCA], [~~http~~://pdbe.org/6bh2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6bh2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6bh2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6bh2 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=6bh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bh2 OCA], [https://pdbe.org/6bh2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bh2 RCSB], [https://www.ebi.ac.uk/pdbsum/6bh2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bh2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KDM5A_HUMAN KDM5A_HUMAN]] Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May stimulate transcription mediated by nuclear receptors. May be involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity).[UniProtKB:Q3UXZ9]<ref>PMID:11358960</ref> <ref>PMID:15949438</ref> <ref>PMID:17320160</ref> <ref>PMID:17320161</ref> <ref>PMID:17320163</ref>	+	[https://www.uniprot.org/uniprot/KDM5A_HUMAN KDM5A_HUMAN] Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May stimulate transcription mediated by nuclear receptors. May be involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity).[UniProtKB:Q3UXZ9]<ref>PMID:11358960</ref> <ref>PMID:15949438</ref> <ref>PMID:17320160</ref> <ref>PMID:17320161</ref> <ref>PMID:17320163</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Jumonji domain-containing protein 3D structures\|Jumonji domain-containing protein 3D structures]]		*[[Jumonji domain-containing protein 3D structures\|Jumonji domain-containing protein 3D structures]]
		+	*[[Lysine-specific histone demethylase 3D structures\|Lysine-specific histone demethylase 3D structures]]
	*[[Retinoblastoma-binding protein 3D structures\|Retinoblastoma-binding protein 3D structures]]		*[[Retinoblastoma-binding protein 3D structures\|Retinoblastoma-binding protein 3D structures]]
	== References ==		== References ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cheng, X]]	+	[[Category: Cheng X]]
-	[[Category: Horton~~, J R]]~~	+	[[Category: Horton JR]]
-	~~[[Category: Demethylase inhibition]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-inhibitor complex]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 10:20, 1 January 2020

2020-01-01T10:20:33Z

←Older revision		Revision as of 10:20, 1 January 2020
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	==LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)-N-(1-(3-isopropyl-1H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropanecarboxamide (Compound N54)==		==LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)-N-(1-(3-isopropyl-1H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropanecarboxamide (Compound N54)==
-	<StructureSection load='6bh2' size='340' side='right' caption='[[6bh2]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='6bh2' size='340' side='right'caption='[[6bh2]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6bh2]] 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=6BH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BH2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6bh2]] 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=6BH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BH2 FirstGlance]. <br>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6bh2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6bh2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Jumonji domain-containing protein 3D structures\|Jumonji domain-containing protein 3D structures]]
		+	*[[Retinoblastoma-binding protein 3D structures\|Retinoblastoma-binding protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cheng, X]]		[[Category: Cheng, X]]
	[[Category: Horton, J R]]		[[Category: Horton, J R]]

OCA at 06:00, 25 April 2018

2018-04-25T06:00:04Z

←Older revision		Revision as of 06:00, 25 April 2018
Line 3:		Line 3:
	<StructureSection load='6bh2' size='340' side='right' caption='[[6bh2]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='6bh2' size='340' side='right' caption='[[6bh2]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bh2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BH2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bh2]] 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=6BH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BH2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90V:N-{(3R)-1-[3-(PROPAN-2-YL)-1H-PYRAZOLE-5-CARBONYL]PYRROLIDIN-3-YL}CYCLOPROPANECARBOXAMIDE'>90V</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90V:N-{(3R)-1-[3-(PROPAN-2-YL)-1H-PYRAZOLE-5-CARBONYL]PYRROLIDIN-3-YL}CYCLOPROPANECARBOXAMIDE'>90V</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDM5A, JARID1A, RBBP2, RBP2 ([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=6bh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bh2 OCA], [http://pdbe.org/6bh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bh2 RCSB], [http://www.ebi.ac.uk/pdbsum/6bh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bh2 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=6bh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bh2 OCA], [http://pdbe.org/6bh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bh2 RCSB], [http://www.ebi.ac.uk/pdbsum/6bh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bh2 ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Cheng, X]]		[[Category: Cheng, X]]
	[[Category: Horton, J R]]		[[Category: Horton, J R]]

OCA at 06:38, 28 March 2018

2018-03-28T06:38:06Z

←Older revision		Revision as of 06:38, 28 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6bh2 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)-N-(1-(3-isopropyl-1H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropanecarboxamide (Compound N54)==
		+	<StructureSection load='6bh2' size='340' side='right' caption='[[6bh2]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6bh2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BH2 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90V:N-{(3R)-1-[3-(PROPAN-2-YL)-1H-PYRAZOLE-5-CARBONYL]PYRROLIDIN-3-YL}CYCLOPROPANECARBOXAMIDE'>90V</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=6bh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bh2 OCA], [http://pdbe.org/6bh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bh2 RCSB], [http://www.ebi.ac.uk/pdbsum/6bh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bh2 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KDM5A_HUMAN KDM5A_HUMAN]] Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May stimulate transcription mediated by nuclear receptors. May be involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity).[UniProtKB:Q3UXZ9]<ref>PMID:11358960</ref> <ref>PMID:15949438</ref> <ref>PMID:17320160</ref> <ref>PMID:17320161</ref> <ref>PMID:17320163</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Isomers of chiral drugs can exhibit marked differences in biological activities. We studied the binding and inhibitory activities of 12 compounds against KDM5A. Among them are two pairs of enantiomers representing two distinct inhibitor chemotypes, namely, ( R)- and ( S)-2-((2-chlorophenyl)(2-(piperidin-1-yl)ethoxy)methyl)-1 H-pyrrolo[3,2- b]pyridine-7-carboxylic acid (compounds N51 and N52) and ( R) - and ( S) -N-(1-(3-isopropyl-1 H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropanecarboxamide (compounds N54 and N55). In vitro, the S enantiomer of the N51/N52 pair (N52) and the R enantiomer of the N54/N55 pair (N54) exhibited about 4- to 5-fold greater binding affinity. The more potent enzyme inhibition of KDM5A by the R-isoform for the cell-permeable N54/N55 pair translated to differences in growth inhibitory activity. We determined structures of the KDM5A catalytic domain in complex with all 12 inhibitors, which revealed the interactions (or lack thereof) responsible for the differences in binding affinity. These results provide insights to guide improvements in binding potency and avenues for development of cell permeable inhibitors of the KDM5 family.

-	~~Authors:~~ Horton, J~~.R.~~, ~~Cheng~~, X.	+	Insights into the Action of Inhibitor Enantiomers against Histone Lysine Demethylase 5A.,Horton JR, Liu X, Wu L, Zhang K, Shanks J, Zhang X, Rai G, Mott BT, Jansen DJ, Kales SC, Henderson MJ, Pohida K, Fang Y, Hu X, Jadhav A, Maloney DJ, Hall MD, Simeonov A, Fu H, Vertino PM, Yan Q, Cheng X J Med Chem. 2018 Mar 23. doi: 10.1021/acs.jmedchem.8b00261. PMID:29537847<ref>PMID:29537847</ref>

-	~~Description: LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)~~-N-~~(1-(3-isopropyl-1H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropanecarboxamide (Compound N54)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 6bh2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Cheng, X]]		[[Category: Cheng, X]]
-	[[Category: Horton, J.R]]	+	[[Category: Horton, J R]]
		+	[[Category: Demethylase inhibition]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-inhibitor complex]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 04:57, 20 December 2017

2017-12-20T04:57:19Z

←Older revision		Revision as of 04:57, 20 December 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6bh2 is ON HOLD	+	The entry 6bh2 is ON HOLD until Paper Publication

	Authors: Horton, J.R., Cheng, X.		Authors: Horton, J.R., Cheng, X.

OCA: Protected "6bh2" [edit=sysop:move=sysop]

2017-11-08T06:35:09Z

Protected "6bh2" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:35, 8 November 2017

OCA: New page: '''Unreleased structure''' The entry 6bh2 is ON HOLD Authors: Horton, J.R., Cheng, X. Description: LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)-N-(1-(3-isopropyl-1H-pyrazole-5-ca...

2017-11-08T06:35:07Z

New page: '''Unreleased structure''' The entry 6bh2 is ON HOLD Authors: Horton, J.R., Cheng, X. Description: LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)-N-(1-(3-isopropyl-1H-pyrazole-5-ca...

New page

'''Unreleased structure'''

The entry 6bh2 is ON HOLD

Authors: Horton, J.R., Cheng, X.

Description: LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)-N-(1-(3-isopropyl-1H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropanecarboxamide (Compound N54)
[[Category: Unreleased Structures]]
[[Category: Cheng, X]]
[[Category: Horton, J.R]]