7rwg - Revision history

OCA at 16:39, 18 October 2023

2023-10-18T16:39:50Z

←Older revision		Revision as of 16:39, 18 October 2023
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	<StructureSection load='7rwg' size='340' side='right'caption='[[7rwg]], [[Resolution\|resolution]] 0.97Å' scene=''>		<StructureSection load='7rwg' size='340' side='right'caption='[[7rwg]], [[Resolution\|resolution]] 0.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7rwg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RWG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7rwg]] 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=7RWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RWG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7UN:(8R)-8-(4-chlorophenyl)-6-(2-methyl-2H-indazol-5-yl)-2-[(2,2,2-trifluoroethyl)amino]-5,8-dihydropyrido[4,3-d]pyrimidin-7(6H)-one'>7UN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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]] 0.97Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7kcc\|7kcc]], [[7rw5\|7rw5]], [[7rw7\|7rw7]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7UN:(8R)-8-(4-chlorophenyl)-6-(2-methyl-2H-indazol-5-yl)-2-[(2,2,2-trifluoroethyl)amino]-5,8-dihydropyrido[4,3-d]pyrimidin-7(6H)-one'>7UN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=7rwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rwg OCA], [https://pdbe.org/7rwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rwg RCSB], [https://www.ebi.ac.uk/pdbsum/7rwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rwg 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=7rwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rwg OCA], [https://pdbe.org/7rwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rwg RCSB], [https://www.ebi.ac.uk/pdbsum/7rwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rwg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.	+	[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Methionine adenosyltransferase]]~~	+	[[Category: Jin L]]
-	[[Category: Jin, L]]	+	[[Category: Padyana AK]]
-	[[Category: Padyana~~, A K]]~~	+
-	~~[[Category: Allosteric inhibitor]]~~	+
-	~~[[Category: Sam]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-inhibitor complex~~]]	+

OCA at 11:16, 30 March 2022

2022-03-30T11:16:59Z

←Older revision		Revision as of 11:16, 30 March 2022
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	=="Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric inhibitor AGI-43192==		=="Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric inhibitor AGI-43192==
-	<StructureSection load='7rwg' size='340' side='right'caption='[[7rwg]]' scene=''>	+	<StructureSection load='7rwg' size='340' side='right'caption='[[7rwg]], [[Resolution\|resolution]] 0.97Å' 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=7RWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RWG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7rwg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RWG 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=7rwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rwg OCA], [https://pdbe.org/7rwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rwg RCSB], [https://www.ebi.ac.uk/pdbsum/7rwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rwg 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=7UN:(8R)-8-(4-chlorophenyl)-6-(2-methyl-2H-indazol-5-yl)-2-[(2,2,2-trifluoroethyl)amino]-5,8-dihydropyrido[4,3-d]pyrimidin-7(6H)-one'>7UN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7kcc\|7kcc]], [[7rw5\|7rw5]], [[7rw7\|7rw7]]</div></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=7rwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rwg OCA], [https://pdbe.org/7rwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rwg RCSB], [https://www.ebi.ac.uk/pdbsum/7rwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rwg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of the S-adenosyl methionine (SAM)-producing metabolic enzyme, methionine adenosyltransferase 2A (MAT2A), has received significant interest in the field of medicinal chemistry due to its implication as a synthetic lethal target in cancers with the deletion of the methylthioadenosine phosphorylase (MTAP) gene. Here, we report the identification of novel MAT2A inhibitors with distinct in vivo properties that may enhance their utility in treating patients. Following a high-throughput screening, we successfully applied the structure-based design lessons from our first-in-class MAT2A inhibitor, AG-270, to rapidly redesign and optimize our initial hit into two new lead compounds: a brain-penetrant compound, AGI-41998, and a potent, but limited brain-penetrant compound, AGI-43192. We hope that the identification and first disclosure of brain-penetrant MAT2A inhibitors will create new opportunities to explore the potential therapeutic effects of SAM modulation in the central nervous system (CNS).
		+
		+	Leveraging Structure-Based Drug Design to Identify Next-Generation MAT2A Inhibitors, Including Brain-Penetrant and Peripherally Efficacious Leads.,Li M, Konteatis Z, Nagaraja N, Chen Y, Zhou S, Ma G, Gross S, Marjon K, Hyer ML, Mandley E, Lein M, Padyana AK, Jin L, Tong S, Peters R, Murtie J, Travins J, Medeiros M, Liu P, Frank V, Judd ET, Biller SA, Marks KM, Sui Z, Reznik SK J Med Chem. 2022 Mar 24;65(6):4600-4615. doi: 10.1021/acs.jmedchem.1c01595. Epub , 2022 Mar 16. PMID:35293760<ref>PMID:35293760</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7rwg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Jin L]]	+	[[Category: Methionine adenosyltransferase]]
-	[[Category: Padyana AK]]	+	[[Category: Jin, L]]
		+	[[Category: Padyana, A K]]
		+	[[Category: Allosteric inhibitor]]
		+	[[Category: Sam]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-inhibitor complex]]

OCA at 11:19, 23 March 2022

2022-03-23T11:19:22Z

←Older revision		Revision as of 11:19, 23 March 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7rwg ~~is ON HOLD until Paper Publication~~	+	=="Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric inhibitor AGI-43192==
-		+	<StructureSection load='7rwg' size='340' side='right'caption='[[7rwg]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RWG 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=7rwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rwg OCA], [https://pdbe.org/7rwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rwg RCSB], [https://www.ebi.ac.uk/pdbsum/7rwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rwg ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Jin L]]
		+	[[Category: Padyana AK]]

OCA at 07:45, 8 September 2021

2021-09-08T07:45:34Z

←Older revision		Revision as of 07:45, 8 September 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

2021-08-25T05:21:40Z

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

←Older revision

Revision as of 05:21, 25 August 2021

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

2021-08-25T05:21:39Z

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

New page

'''Unreleased structure'''

The entry 7rwg is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]