6i9m - Revision history

OCA at 11:51, 1 February 2024

2024-02-01T11:51:17Z

←Older revision		Revision as of 11:51, 1 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6i9m]] 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=6I9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9M FirstGlance]. <br>		<table><tr><td colspan='2'>[[6i9m]] 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=6I9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9M FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2HG:(2R)-2-HYDROXYPENTANEDIOIC+ACID'>2HG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 1.65Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2HG:(2R)-2-HYDROXYPENTANEDIOIC+ACID'>2HG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=6i9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9m OCA], [https://pdbe.org/6i9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9m RCSB], [https://www.ebi.ac.uk/pdbsum/6i9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9m 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=6i9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9m OCA], [https://pdbe.org/6i9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9m RCSB], [https://www.ebi.ac.uk/pdbsum/6i9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9m ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:02, 21 December 2022

2022-12-21T10:02:51Z

←Older revision		Revision as of 10:02, 21 December 2022
Line 3:		Line 3:
	<StructureSection load='6i9m' size='340' side='right'caption='[[6i9m]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='6i9m' size='340' side='right'caption='[[6i9m]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6i9m]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9M OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6I9M FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6i9m]] 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=6I9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9M FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HG:(2R)-2-HYDROXYPENTANEDIOIC+ACID'>2HG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2HG:(2R)-2-HYDROXYPENTANEDIOIC+ACID'>2HG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=6i9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9m OCA], [~~http~~://pdbe.org/6i9m PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6i9m RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6i9m PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9m 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=6i9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9m OCA], [https://pdbe.org/6i9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9m RCSB], [https://www.ebi.ac.uk/pdbsum/6i9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9m ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KDM8_HUMAN KDM8_HUMAN]] Histone demethylase required for G2/M phase cell cycle progression. Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator. Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation.	+	[https://www.uniprot.org/uniprot/KDM8_HUMAN KDM8_HUMAN] Histone demethylase required for G2/M phase cell cycle progression. Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator. Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Oxygenase-catalysed post-translational modifications of basic protein residues, including lysyl hydroxylations and N~~(~~epsilon)-methyl lysyl demethylations, have important cellular roles.~~ Jumonji-C ~~(JmjC~~) domain-containing ~~protein~~ 5 (JMJD5)~~, which genetic studies reveal~~ is ~~essential~~ in ~~animal~~ development, is ~~reported as~~ a histone N(epsilon)-methyl lysine ~~demethylase~~ (~~KDM~~). ~~Here we report how extensive screening with peptides based on~~ JMJD5 ~~interacting proteins led~~ to ~~the finding that JMJD5 catalyses stereoselective~~ C-3 hydroxylation of arginine residues in sequences from human regulator of chromosome condensation domain-containing protein 1 (RCCD1) and ribosomal protein S6 (RPS6). ~~High-resolution~~ crystallographic analyses ~~reveal overall fold~~, ~~active site~~ and ~~substrate binding/product release features supporting~~ the assignment of JMJD5 as ~~an arginine hydroxylase rather than~~ a ~~KDM~~. ~~The results~~ will be useful in the development of ~~selective oxygenase inhibitors for~~ the ~~treatment~~ of ~~cancer~~ and ~~genetic diseases~~.	+	JmjC (Jumonji-C) domain-containing 5 (JMJD5) plays important roles in circadian regulation in plants and humans and is involved in embryonic development and cell proliferation. JMJD5 is a 2-oxoglutarate (2OG) and Fe(II) dependent oxygenase of the JmjC subfamily, which includes histone N(epsilon)-methyl lysine-demethylases (KDMs) and hydroxylases catalysing formation of stable alcohol products. JMJD5 is reported to have KDM activity, but has been shown to catalyse C-3 hydroxylation of arginine residues in sequences from human regulator of chromosome condensation domain-containing protein 1 (RCCD1) and ribosomal protein S6 (RPS6) in vitro. We report crystallographic analyses of human JMJD5 complexed with 2OG analogues, including the widely used hypoxia mimic pyridine-2,4-dicarboxylate, both D- and L-enantiomers of the oncometabolite 2-hydroxyglutarate, and a cyclic N-hydroxyimide. The results support the assignment of JMJD5 as a protein hydroxylase and reveal JMJD5 has an unusually compact 2OG binding pocket suitable for exploitation in development of selective inhibitors. They will be useful in the development of chemical probes to investigate the physiologically relevant roles of JMJD5 in circadian rhythm and development and explore its potential as a medicinal chemistry target.

-	JMJD5 ~~is a human arginyl C-3 hydroxylase~~.~~,Wilkins SE~~, Islam S, ~~Gannon JM~~, ~~Markolovic S, Hopkinson RJ, Ge W~~, Schofield CJ~~, Chowdhury R Nat Commun~~. ~~2018 Mar 21~~;9(1):~~1180~~. doi: 10.1038/~~s41467~~-~~018~~-~~03410~~-w. PMID:~~29563586~~<ref>PMID:~~29563586~~</ref>	+	Structural analysis of the 2-oxoglutarate binding site of the circadian rhythm linked oxygenase JMJD5.,Islam MS, Markoulides M, Chowdhury R, Schofield CJ Sci Rep. 2022 Nov 30;12(1):20680. doi: 10.1038/s41598-022-24154-0. PMID:36450832<ref>PMID:36450832</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>
	</div>		</div>
	<div class="pdbe-citations 6i9m" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6i9m" 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: Chowdhury, R]]	+	[[Category: Chowdhury R]]
-	[[Category: Islam~~, M S~~]]	+	[[Category: Islam MS]]
-	[[Category: Schofield~~, C J]]~~	+	[[Category: Schofield CJ]]
-	~~[[Category: 2-oxoglutarate]]~~	+
-	~~[[Category: 40s ribosomal protein s6]]~~	+
-	~~[[Category: Arginine hydroxylation]]~~	+
-	~~[[Category: Arginyl c-3 hydroxylase]]~~	+
-	~~[[Category: Beta-hydroxylation]]~~	+
-	~~[[Category: Cancer]]~~	+
-	~~[[Category: Cell structure]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Development]]~~	+
-	~~[[Category: Dioxygenase]]~~	+
-	~~[[Category: Dna-binding]]~~	+
-	~~[[Category: Dsbh]]~~	+
-	~~[[Category: Epigenetic regulation]]~~	+
-	~~[[Category: Facial triad]]~~	+
-	~~[[Category: Hydroxylation]]~~	+
-	~~[[Category: Hypoxia]]~~	+
-	~~[[Category: Iron]]~~	+
-	~~[[Category: Jmjc]]~~	+
-	~~[[Category: Jmjc demethylase]]~~	+
-	~~[[Category: Jmjc domain]]~~	+
-	~~[[Category: Jmjc domain-containing protein 5]]~~	+
-	~~[[Category: Jmjc hydroxylase]]~~	+
-	~~[[Category: Jmjd5]]~~	+
-	~~[[Category: Kdm]]~~	+
-	~~[[Category: Kdm8]]~~	+
-	~~[[Category: Lysine-specific demethylase 8]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Non-heme]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxygenase]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Post-translational modification]]~~	+
-	~~[[Category: Ptm]]~~	+
-	~~[[Category: Rcc1 domain-containing protein 1]]~~	+
-	~~[[Category: Rccd1]]~~	+
-	~~[[Category: Regulator of chromosome condensation]]~~	+
-	~~[[Category: Ribosome biogenesis]]~~	+
-	~~[[Category: Rps6]]~~	+
-	~~[[Category: Signaling]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription activator/inhibitor]]~~	+
-	~~[[Category: Translation~~]]	+

OCA at 07:57, 4 December 2019

2019-12-04T07:57:05Z

←Older revision		Revision as of 07:57, 4 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6i9m is ~~ON HOLD~~	+	==JmjC domain-containing protein 5 (JMJD5) in complex with Mn and R-2-hydroxyglutarate==
		+	<StructureSection load='6i9m' size='340' side='right'caption='[[6i9m]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6i9m]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I9M FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HG:(2R)-2-HYDROXYPENTANEDIOIC+ACID'>2HG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=6i9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9m OCA], [http://pdbe.org/6i9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i9m RCSB], [http://www.ebi.ac.uk/pdbsum/6i9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9m ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KDM8_HUMAN KDM8_HUMAN]] Histone demethylase required for G2/M phase cell cycle progression. Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator. Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Oxygenase-catalysed post-translational modifications of basic protein residues, including lysyl hydroxylations and N(epsilon)-methyl lysyl demethylations, have important cellular roles. Jumonji-C (JmjC) domain-containing protein 5 (JMJD5), which genetic studies reveal is essential in animal development, is reported as a histone N(epsilon)-methyl lysine demethylase (KDM). Here we report how extensive screening with peptides based on JMJD5 interacting proteins led to the finding that JMJD5 catalyses stereoselective C-3 hydroxylation of arginine residues in sequences from human regulator of chromosome condensation domain-containing protein 1 (RCCD1) and ribosomal protein S6 (RPS6). High-resolution crystallographic analyses reveal overall fold, active site and substrate binding/product release features supporting the assignment of JMJD5 as an arginine hydroxylase rather than a KDM. The results will be useful in the development of selective oxygenase inhibitors for the treatment of cancer and genetic diseases.

-	~~Authors~~:	+	JMJD5 is a human arginyl C-3 hydroxylase.,Wilkins SE, Islam S, Gannon JM, Markolovic S, Hopkinson RJ, Ge W, Schofield CJ, Chowdhury R Nat Commun. 2018 Mar 21;9(1):1180. doi: 10.1038/s41467-018-03410-w. PMID:29563586<ref>PMID:29563586</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6i9m" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chowdhury, R]]
		+	[[Category: Islam, M S]]
		+	[[Category: Schofield, C J]]
		+	[[Category: 2-oxoglutarate]]
		+	[[Category: 40s ribosomal protein s6]]
		+	[[Category: Arginine hydroxylation]]
		+	[[Category: Arginyl c-3 hydroxylase]]
		+	[[Category: Beta-hydroxylation]]
		+	[[Category: Cancer]]
		+	[[Category: Cell structure]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Development]]
		+	[[Category: Dioxygenase]]
		+	[[Category: Dna-binding]]
		+	[[Category: Dsbh]]
		+	[[Category: Epigenetic regulation]]
		+	[[Category: Facial triad]]
		+	[[Category: Hydroxylation]]
		+	[[Category: Hypoxia]]
		+	[[Category: Iron]]
		+	[[Category: Jmjc]]
		+	[[Category: Jmjc demethylase]]
		+	[[Category: Jmjc domain]]
		+	[[Category: Jmjc domain-containing protein 5]]
		+	[[Category: Jmjc hydroxylase]]
		+	[[Category: Jmjd5]]
		+	[[Category: Kdm]]
		+	[[Category: Kdm8]]
		+	[[Category: Lysine-specific demethylase 8]]
		+	[[Category: Metal-binding]]
		+	[[Category: Non-heme]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxygenase]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Polymorphism]]
		+	[[Category: Post-translational modification]]
		+	[[Category: Ptm]]
		+	[[Category: Rcc1 domain-containing protein 1]]
		+	[[Category: Rccd1]]
		+	[[Category: Regulator of chromosome condensation]]
		+	[[Category: Ribosome biogenesis]]
		+	[[Category: Rps6]]
		+	[[Category: Signaling]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription activator/inhibitor]]
		+	[[Category: Translation]]

OCA: Protected "6i9m" [edit=sysop:move=sysop]

2018-12-05T04:59:52Z

Protected "6i9m" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:59, 5 December 2018

OCA: New page: '''Unreleased structure''' The entry 6i9m is ON HOLD Authors: Description: Category: Unreleased Structures

2018-12-05T04:59:51Z

New page: '''Unreleased structure''' The entry 6i9m is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6i9m is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]