7p2r - Revision history

OCA at 13:00, 1 February 2024

OCA — Thu, 01 Feb 2024 13:00:31 GMT

←Older revision		Revision as of 13:00, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7p2r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2R FirstGlance]. <br>		<table><tr><td colspan='2'>[[7p2r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2R FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4R7:methyl+6-[4-[[N-[2-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]ethyl]carbamimidoyl]amino]butylcarbamoylamino]-4-oxidanyl-naphthalene-2-carboxylate'>4R7</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 2.3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4R7:methyl+6-[4-[[N-[2-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]ethyl]carbamimidoyl]amino]butylcarbamoylamino]-4-oxidanyl-naphthalene-2-carboxylate'>4R7</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=7p2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2r OCA], [https://pdbe.org/7p2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2r RCSB], [https://www.ebi.ac.uk/pdbsum/7p2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2r 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=7p2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2r OCA], [https://pdbe.org/7p2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2r RCSB], [https://www.ebi.ac.uk/pdbsum/7p2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2r ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/ANM6_MOUSE ANM6_MOUSE]] Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. Repression of TP53 blocks cellular senescence. Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity. Methylates HMGA1. Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator.<ref>PMID:22904064</ref> <ref>PMID:24570487</ref>	+	[https://www.uniprot.org/uniprot/ANM6_MOUSE ANM6_MOUSE] Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. Repression of TP53 blocks cellular senescence. Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity. Methylates HMGA1. Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator.<ref>PMID:22904064</ref> <ref>PMID:24570487</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7p2r" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7p2r" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:52, 21 September 2022

OCA — Wed, 21 Sep 2022 07:52:50 GMT

←Older revision		Revision as of 07:52, 21 September 2022
Line 1:		Line 1:

	==Crystal structure of mouse PRMT6 in complex with inhibitor EML980==		==Crystal structure of mouse PRMT6 in complex with inhibitor EML980==
-	<StructureSection load='7p2r' size='340' side='right'caption='[[7p2r]]' scene=''>	+	<StructureSection load='7p2r' size='340' side='right'caption='[[7p2r]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7p2r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2R FirstGlance]. <br>
-	</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=7p2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2r OCA], [https://pdbe.org/7p2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2r RCSB], [https://www.ebi.ac.uk/pdbsum/7p2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2r ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4R7:methyl+6-[4-[[N-[2-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]ethyl]carbamimidoyl]amino]butylcarbamoylamino]-4-oxidanyl-naphthalene-2-carboxylate'>4R7</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=7p2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2r OCA], [https://pdbe.org/7p2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2r RCSB], [https://www.ebi.ac.uk/pdbsum/7p2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2r ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/ANM6_MOUSE ANM6_MOUSE]] Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. Repression of TP53 blocks cellular senescence. Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity. Methylates HMGA1. Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator.<ref>PMID:22904064</ref> <ref>PMID:24570487</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein arginine methyltransferases (PRMTs) are important therapeutic targets, playing a crucial role in the regulation of many cellular processes and being linked to many diseases. Yet, there is still much to be understood regarding their functions and the biological pathways in which they are involved, as well as on the structural requirements that could drive the development of selective modulators of PRMT activity. Here we report a deconstruction-reconstruction approach that, starting from a series of type I PRMT inhibitors previously identified by us, allowed for the identification of potent and selective inhibitors of PRMT4, which regardless of the low cell permeability show an evident reduction of arginine methylation levels in MCF7 cells and a marked reduction of proliferation. We also report crystal structures with various PRMTs supporting the observed specificity and selectivity.
		+
		+	Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction-Reconstruction and Fragment-Growing Approach.,Iannelli G, Milite C, Marechal N, Cura V, Bonnefond L, Troffer-Charlier N, Feoli A, Rescigno D, Wang Y, Cipriano A, Viviano M, Bedford MT, Cavarelli J, Castellano S, Sbardella G J Med Chem. 2022 Apr 28. doi: 10.1021/acs.jmedchem.2c00252. PMID:35482954<ref>PMID:35482954</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7p2r" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Mus musculus]]
	[[Category: Bonnefond L]]		[[Category: Bonnefond L]]
	[[Category: Cavarelli J]]		[[Category: Cavarelli J]]

OCA at 06:18, 12 May 2022

OCA — Thu, 12 May 2022 06:18:33 GMT

←Older revision		Revision as of 06:18, 12 May 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7p2r ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of mouse PRMT6 in complex with inhibitor EML980==
-		+	<StructureSection load='7p2r' size='340' side='right'caption='[[7p2r]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2R FirstGlance]. <br>
-	~~Description~~:	+	</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=7p2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2r OCA], [https://pdbe.org/7p2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2r RCSB], [https://www.ebi.ac.uk/pdbsum/7p2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2r ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bonnefond L]]
		+	[[Category: Cavarelli J]]

OCA at 13:50, 22 December 2021

OCA — Wed, 22 Dec 2021 13:50:38 GMT

←Older revision		Revision as of 13:50, 22 December 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7p2r is ON HOLD	+	The entry 7p2r is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 15:29, 15 December 2021

OCA — Wed, 15 Dec 2021 15:29:13 GMT

←Older revision		Revision as of 15:29, 15 December 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7p2r is ON HOLD ~~until Paper Publication~~	+	The entry 7p2r is ON HOLD

	Authors:		Authors:

OCA: Protected "7p2r" [edit=sysop:move=sysop]

OCA — Wed, 14 Jul 2021 08:52:08 GMT

Protected "7p2r" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:52, 14 July 2021

OCA: New page: '''Unreleased structure''' The entry 7p2r is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 14 Jul 2021 08:52:07 GMT

New page: '''Unreleased structure''' The entry 7p2r is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7p2r is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]