5ivy - Revision history

OCA at 10:33, 6 September 2023

OCA — Wed, 06 Sep 2023 10:33:57 GMT

←Older revision		Revision as of 10:33, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='5ivy' size='340' side='right'caption='[[5ivy]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='5ivy' size='340' side='right'caption='[[5ivy]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ivy]] 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=5IVY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5IVY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ivy]] 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=5IVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IVY FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=6EO:3~~-{[~~(4-CHLOROPHENYL)ACETYL~~]~~AMINO}PYRIDINE-4-CARBOXYLIC+ACID'>6EO</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]] 1.45Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">[~~[5isl\|5isl~~]~~], [[5isb\|5isb]], [[5ivc\|5ivc]], [[5ive\|5ive]], [[5ivf\|5ivf]], [[5ivj\|5ivj]], [[5ivv\|5ivv]], [[5iw0\|5iw0]], [[5iwf\|5iwf]]</td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6EO:3-{[(4-CHLOROPHENYL)ACETYL]AMINO}PYRIDINE-4-CARBOXYLIC+ACID'>6EO</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'>[https://proteopedia.org/fgij/fg.htm?mol=5ivy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ivy OCA], [https://pdbe.org/5ivy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ivy RCSB], [https://www.ebi.ac.uk/pdbsum/5ivy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ivy 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=5ivy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ivy OCA], [~~http~~://pdbe.org/5ivy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ivy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ivy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ivy 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 ==
Line 23:		Line 22:
	==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]]
	== References ==		== References ==
	<references/>		<references/>
	__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-oxidoreductase inhibitor complex~~]]	+

OCA at 07:19, 10 June 2020

OCA — Wed, 10 Jun 2020 07:19:02 GMT

←Older revision		Revision as of 07:19, 10 June 2020
Line 1:		Line 1:

	==Linked KDM5A Jmj Domain Bound to the Inhibitor N16 [3-(2-(4-chlorophenyl)acetamido)isonicotinic acid]==		==Linked KDM5A Jmj Domain Bound to the Inhibitor N16 [3-(2-(4-chlorophenyl)acetamido)isonicotinic acid]==
-	<StructureSection load='5ivy' size='340' side='right' caption='[[5ivy]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='5ivy' size='340' side='right'caption='[[5ivy]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ivy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IVY OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5IVY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ivy]] 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=5IVY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IVY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6EO:3-{[(4-CHLOROPHENYL)ACETYL]AMINO}PYRIDINE-4-CARBOXYLIC+ACID'>6EO</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" id="ligandDat"><scene name='pdbligand=6EO:3-{[(4-CHLOROPHENYL)ACETYL]AMINO}PYRIDINE-4-CARBOXYLIC+ACID'>6EO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5isl\|5isl]], [[5isb\|5isb]], [[5ivc\|5ivc]], [[5ive\|5ive]], [[5ivf\|5ivf]], [[5ivj\|5ivj]], [[5ivv\|5ivv]], [[5iw0\|5iw0]], [[5iwf\|5iwf]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5isl\|5isl]], [[5isb\|5isb]], [[5ivc\|5ivc]], [[5ive\|5ive]], [[5ivf\|5ivf]], [[5ivj\|5ivj]], [[5ivv\|5ivv]], [[5iw0\|5iw0]], [[5iwf\|5iwf]]</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=5ivy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ivy OCA], [http://pdbe.org/5ivy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ivy RCSB], [http://www.ebi.ac.uk/pdbsum/5ivy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ivy ProSAT]</span></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://proteopedia.org/fgij/fg.htm?mol=5ivy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ivy OCA], [http://pdbe.org/5ivy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ivy RCSB], [http://www.ebi.ac.uk/pdbsum/5ivy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ivy ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5ivy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ivy" 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: Cheng, X]]		[[Category: Cheng, X]]
	[[Category: Horton, J R]]		[[Category: Horton, J R]]
	[[Category: Demethylase inhibition]]		[[Category: Demethylase inhibition]]
	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]		[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 20:36, 3 August 2016

OCA — Wed, 03 Aug 2016 20:36:12 GMT

←Older revision		Revision as of 20:36, 3 August 2016
Line 12:		Line 12:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	The KDM5/JARID1 family of Fe(II)- and alpha-ketoglutarate-dependent demethylases ~~remove~~ methyl groups from ~~tri- and di-~~methylated lysine 4 of histone H3. Accumulating evidence ~~from primary tumors and model systems support~~ a role for ~~KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1)~~ as oncogenic drivers. ~~The KDM5 family is unique among~~ the ~~Jumonji domain-containing histone demethylases~~ in ~~that there is an atypical insertion of a DNA-binding ARID domain~~ and ~~a histone-~~binding ~~PHD domain into the Jumonji domain~~, ~~which separates the catalytic domain into two fragments (JmjN~~ and ~~JmjC). Here we demonstrate that internal deletion of~~ the ~~ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes. We present a~~ crystal ~~structure~~ of the ~~linked JmjN~~-~~JmjC domain from KDM5A, which reveals that the~~ linked ~~domain fully reconstitutes the cofactor (metal ion and alpha-ketoglutarate) binding characteristics of other structurally-characterized~~ Jumonji domain ~~demethylases. Docking studies~~ with ~~GSK-J1, a selective inhibitor~~ of the ~~KDM6/KDM5 sub-families, identify critical residues for binding~~ of ~~the inhibitor to the reconstituted KDM5 Jumonji domain~~. ~~Further, we found that GSK-J1 inhibited~~ the ~~demethylase activity~~ of ~~KDM5C with 8.5-fold increased potency compared to that of KDM5B at 1 mM~~ alpha-ketoglutarate~~. In contrast~~, ~~JIB-04 (a pan-inhibitor of the Jumonji demethylase superfamily) had the opposite effect and was approximately 8-fold more potent against KDM5B than KDM5C. Interestingly~~, the ~~relative selectivity~~ of ~~JIB-04 towards KDM5B over KDM5C~~ in ~~vitro translates to a ~10-50-fold greater growth inhibitory activity against breast cancer cell lines~~. ~~These data define the minimal requirements for enzymatic activity of the KDM5 family to be the linked JmjN~~-~~JmjC domain coupled with~~ the ~~immediate C- terminal helical Zn-~~binding ~~domain and provide structural characterization~~ of ~~the linked JmjN~~-~~JmjC domain for~~ the ~~KDM5 family~~, ~~which should prove useful~~ in the design of ~~KDM5 demethylase inhibitors with improved potency~~ and ~~selectivity~~.	+	The KDM5/JARID1 family of Fe(II)- and alpha-ketoglutarate-dependent demethylases removes methyl groups from methylated lysine 4 of histone H3. Accumulating evidence supports a role for KDM5 family members as oncogenic drivers. We compare the in vitro inhibitory properties and binding affinity of ten diverse compounds with all four family members, and present the crystal structures of the KDM5A-linked Jumonji domain in complex with eight of these inhibitors in the presence of Mn(II). All eight inhibitors structurally examined occupy the binding site of alpha-ketoglutarate, but differ in their specific binding interactions, including the number of ligands involved in metal coordination. We also observed inhibitor-induced conformational changes in KDM5A, particularly those residues involved in the binding of alpha-ketoglutarate, the anticipated peptide substrate, and intramolecular interactions. We discuss how particular chemical moieties contribute to inhibitor potency and suggest strategies that might be utilized in the successful design of selective and potent epigenetic inhibitors.

-	~~Characterization of a linked Jumonji domain of the KDM5/JARID1 family of histone H3 lysine 4 demethylases~~.,Horton JR~~, Engstrom A, Zoeller EL~~, Liu X, Shanks JR, Zhang X, Johns MA, Vertino PM, ~~Fu H~~, Cheng X ~~J Biol~~ Chem. ~~2015 Dec 8~~. ~~pii~~: ~~jbc~~.~~M115~~.~~698449~~. PMID:~~26645689~~<ref>PMID:~~26645689~~</ref>	+	Structural Basis for KDM5A Histone Lysine Demethylase Inhibition by Diverse Compounds.,Horton JR, Liu X, Gale M, Wu L, Shanks JR, Zhang X, Webber PJ, Bell JS, Kales SC, Mott BT, Rai G, Jansen DJ, Henderson MJ, Urban DJ, Hall MD, Simeonov A, Maloney DJ, Johns MA, Fu H, Jadhav A, Vertino PM, Yan Q, Cheng X Cell Chem Biol. 2016 Jul 21;23(7):769-81. doi: 10.1016/j.chembiol.2016.06.006., Epub 2016 Jul 14. PMID:27427228<ref>PMID:27427228</ref>

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

OCA at 15:44, 27 July 2016

OCA — Wed, 27 Jul 2016 15:44:46 GMT

←Older revision		Revision as of 15:44, 27 July 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ivy is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Linked KDM5A Jmj Domain Bound to the Inhibitor N16 [3-(2-(4-chlorophenyl)acetamido)isonicotinic acid]==
		+	<StructureSection load='5ivy' size='340' side='right' caption='[[5ivy]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ivy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IVY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IVY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6EO:3-{[(4-CHLOROPHENYL)ACETYL]AMINO}PYRIDINE-4-CARBOXYLIC+ACID'>6EO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5isl\|5isl]], [[5isb\|5isb]], [[5ivc\|5ivc]], [[5ive\|5ive]], [[5ivf\|5ivf]], [[5ivj\|5ivj]], [[5ivv\|5ivv]], [[5iw0\|5iw0]], [[5iwf\|5iwf]]</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=5ivy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ivy OCA], [http://pdbe.org/5ivy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ivy RCSB], [http://www.ebi.ac.uk/pdbsum/5ivy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ivy 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 ==
		+	The KDM5/JARID1 family of Fe(II)- and alpha-ketoglutarate-dependent demethylases remove methyl groups from tri- and di-methylated lysine 4 of histone H3. Accumulating evidence from primary tumors and model systems support a role for KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) as oncogenic drivers. The KDM5 family is unique among the Jumonji domain-containing histone demethylases in that there is an atypical insertion of a DNA-binding ARID domain and a histone-binding PHD domain into the Jumonji domain, which separates the catalytic domain into two fragments (JmjN and JmjC). Here we demonstrate that internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes. We present a crystal structure of the linked JmjN-JmjC domain from KDM5A, which reveals that the linked domain fully reconstitutes the cofactor (metal ion and alpha-ketoglutarate) binding characteristics of other structurally-characterized Jumonji domain demethylases. Docking studies with GSK-J1, a selective inhibitor of the KDM6/KDM5 sub-families, identify critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. Further, we found that GSK-J1 inhibited the demethylase activity of KDM5C with 8.5-fold increased potency compared to that of KDM5B at 1 mM alpha-ketoglutarate. In contrast, JIB-04 (a pan-inhibitor of the Jumonji demethylase superfamily) had the opposite effect and was approximately 8-fold more potent against KDM5B than KDM5C. Interestingly, the relative selectivity of JIB-04 towards KDM5B over KDM5C in vitro translates to a ~10-50-fold greater growth inhibitory activity against breast cancer cell lines. These data define the minimal requirements for enzymatic activity of the KDM5 family to be the linked JmjN-JmjC domain coupled with the immediate C- terminal helical Zn-binding domain and provide structural characterization of the linked JmjN-JmjC domain for the KDM5 family, which should prove useful in the design of KDM5 demethylase inhibitors with improved potency and selectivity.

-	~~Authors:~~ Horton, ~~J.R.~~, ~~Cheng~~, X.	+	Characterization of a linked Jumonji domain of the KDM5/JARID1 family of histone H3 lysine 4 demethylases.,Horton JR, Engstrom A, Zoeller EL, Liu X, Shanks JR, Zhang X, Johns MA, Vertino PM, Fu H, Cheng X J Biol Chem. 2015 Dec 8. pii: jbc.M115.698449. PMID:26645689<ref>PMID:26645689</ref>

-	~~Description: Linked KDM5A Jmj Domain Bound to~~ the ~~Inhibitor N16 [3~~-(2-~~(4-chlorophenyl)acetamido)isonicotinic acid]~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Horton, J.R]]~~	+	<div class="pdbe-citations 5ivy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Cheng, X]]		[[Category: Cheng, X]]
		+	[[Category: Horton, J R]]
		+	[[Category: Demethylase inhibition]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA: Protected "5ivy" [edit=sysop:move=sysop]

OCA — Wed, 11 May 2016 01:02:50 GMT

Protected "5ivy" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:02, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5ivy is ON HOLD until Paper Publication Authors: Horton, J.R., Cheng, X. Description: Linked KDM5A Jmj Domain Bound to the Inhibitor N16 [3-(2-(4-c...

OCA — Wed, 11 May 2016 01:02:48 GMT

New page: '''Unreleased structure''' The entry 5ivy is ON HOLD until Paper Publication Authors: Horton, J.R., Cheng, X. Description: Linked KDM5A Jmj Domain Bound to the Inhibitor N16 [3-(2-(4-c...

New page

'''Unreleased structure'''

The entry 5ivy is ON HOLD until Paper Publication

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

Description: Linked KDM5A Jmj Domain Bound to the Inhibitor N16 [3-(2-(4-chlorophenyl)acetamido)isonicotinic acid]
[[Category: Unreleased Structures]]
[[Category: Horton, J.R]]
[[Category: Cheng, X]]