OCA at 15:36, 18 October 2023

2023-10-18T15:36:09Z

←Older revision		Revision as of 15:36, 18 October 2023
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-	====	+	==PRMT5-MEP50 Complexed with SAM==
-	<StructureSection load='7l1g' size='340' side='right'caption='[[7l1g]]' scene=''>	+	<StructureSection load='7l1g' size='340' side='right'caption='[[7l1g]], [[Resolution\|resolution]] 2.47Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7l1g]] 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=7L1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L1G 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=7l1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l1g OCA], [https://pdbe.org/7l1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l1g RCSB], [https://www.ebi.ac.uk/pdbsum/7l1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l1g ProSAT]</span></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]] 2.47Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=7l1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l1g OCA], [https://pdbe.org/7l1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l1g RCSB], [https://www.ebi.ac.uk/pdbsum/7l1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l1g ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/ANM5_HUMAN ANM5_HUMAN] Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Methylates SUPT5H. Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. Plays a role in the assembly of snRNP core particles. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. May regulate the SUPT5H transcriptional elongation properties. May be part of a pathway that is connected to a chloride current, possibly through cytoskeletal rearrangement. Methylates histone H2A and H4 'Arg-3' during germ cell development. Methylates histone H3 'Arg-8', which may repress transcription. Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage. Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity. Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation. Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter.<ref>PMID:10531356</ref> <ref>PMID:11152681</ref> <ref>PMID:11747828</ref> <ref>PMID:12411503</ref> <ref>PMID:15737618</ref> <ref>PMID:17709427</ref> <ref>PMID:20159986</ref> <ref>PMID:20810653</ref> <ref>PMID:21258366</ref> <ref>PMID:21917714</ref> <ref>PMID:22269951</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In the context of a PRMT5 inhibitor program, we describe our efforts to develop a flexible and robust strategy to access tetrahydrofuro[3,4-b]furan nucleoside analogues. Ultimately, it was found that a Wolfe type carboetherification from an alkenol derived from d-glucofuranose diacetonide was capable of furnishing the B-ring and installing the desired heteroaryl group in a single step. Using this approach, key intermediate 1.3-A was delivered on a gram scale in a 62% yield and 9.1:1 dr in favor of the desired S-isomer. After deprotection of 1.3-A, a late-stage glycosylation was performed under Mitsunobu conditions to install the pyrrolopyrimidine base. This provided serviceable yields of nucleoside analogues in the range of 31-48% yield. Compound 1.1-C was profiled in biochemical and cellular assays and was demonstrated to be a potent and cellularly active PRMT5 inhibitor, with a PRMT5-MEP50 biochemical IC(50) of 0.8 nM, a MCF-7 target engagement EC(50) of 3 nM, and a Z138 cell proliferation EC(50) of 15 nM. This work sets the stage for the development of new inhibitors of PRMT5 and novel nucleoside chemical matter for alternate drug discovery programs.
		+
		+	Development of a Flexible and Robust Synthesis of Tetrahydrofuro[3,4-b]furan Nucleoside Analogues.,Candito DA, Ye Y, Quiroz RV, Reutershan MH, Witter D, Gadamsetty SB, Li H, Sauri J, Schneider SE, Lam YH, Palte RL J Org Chem. 2021 Apr 2;86(7):5142-5151. doi: 10.1021/acs.joc.0c02969. Epub 2021 , Mar 23. PMID:33755465<ref>PMID:33755465</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7l1g" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Palte RL]]

OCA at 06:47, 14 April 2021

2021-04-14T06:47:56Z

←Older revision		Revision as of 06:47, 14 April 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7l1g ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7l1g' size='340' side='right'caption='[[7l1g]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= 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=7l1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l1g OCA], [https://pdbe.org/7l1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l1g RCSB], [https://www.ebi.ac.uk/pdbsum/7l1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l1g ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 06:51, 20 January 2021

2021-01-20T06:51:32Z

←Older revision		Revision as of 06:51, 20 January 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7l1g is ON HOLD	+	The entry 7l1g is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7l1g" [edit=sysop:move=sysop]

2020-12-24T08:08:40Z

Protected "7l1g" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:08, 24 December 2020

OCA: New page: '''Unreleased structure''' The entry 7l1g is ON HOLD Authors: Description: Category: Unreleased Structures

2020-12-24T08:08:38Z

New page: '''Unreleased structure''' The entry 7l1g is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7l1g is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7l1g - Revision history

OCA at 15:36, 18 October 2023

OCA at 06:47, 14 April 2021

OCA at 06:51, 20 January 2021

OCA: Protected "7l1g" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7l1g is ON HOLD Authors: Description: Category: Unreleased Structures