7kce - Revision history

OCA at 15:21, 18 October 2023

OCA — Wed, 18 Oct 2023 15:21:12 GMT

←Older revision		Revision as of 15:21, 18 October 2023
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	<StructureSection load='7kce' size='340' side='right'caption='[[7kce]], [[Resolution\|resolution]] 1.14Å' scene=''>		<StructureSection load='7kce' size='340' side='right'caption='[[7kce]], [[Resolution\|resolution]] 1.14Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7kce]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KCE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kce]] 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=7KCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KCE FirstGlance]. <br>
-	</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=J41:5-methyl-2,3-diphenylpyrazolo[1,5-a]pyrimidin-7(4H)-one'>J41</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]] 1.14Å</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]], [[7kcf\|7kcf]], [[7kda\|7kda]], [[7kdb\|7kdb]]</div></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=J41:5-methyl-2,3-diphenylpyrazolo[1,5-a]pyrimidin-7(4H)-one'>J41</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=7kce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kce OCA], [https://pdbe.org/7kce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kce RCSB], [https://www.ebi.ac.uk/pdbsum/7kce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kce 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=7kce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kce OCA], [https://pdbe.org/7kce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kce RCSB], [https://www.ebi.ac.uk/pdbsum/7kce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kce 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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	</div>		</div>
	<div class="pdbe-citations 7kce" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7kce" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[S-adenosylmethionine synthetase 3D structures\|S-adenosylmethionine synthetase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Methionine adenosyltransferase]]~~	+	[[Category: Jin L]]
-	[[Category: Jin, L]]	+	[[Category: Padyana A]]
-	[[Category: Padyana, A]]	+
-	~~[[Category: Allosteric inhibitor]]~~	+
-	~~[[Category: S-adenosylmethionine synthase isoform type-2]]~~	+
-	~~[[Category: Sam]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-inhibitor complex~~]]	+

OCA at 09:12, 5 May 2021

OCA — Wed, 05 May 2021 09:12:35 GMT

←Older revision		Revision as of 09:12, 5 May 2021
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	==Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric inhibitor compound 2==		==Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric inhibitor compound 2==
-	<StructureSection load='7kce' size='340' side='right'caption='[[7kce]]' scene=''>	+	<StructureSection load='7kce' size='340' side='right'caption='[[7kce]], [[Resolution\|resolution]] 1.14Å' 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=7KCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KCE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kce]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KCE 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=7kce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kce OCA], [https://pdbe.org/7kce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kce RCSB], [https://www.ebi.ac.uk/pdbsum/7kce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kce 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=J41:5-methyl-2,3-diphenylpyrazolo[1,5-a]pyrimidin-7(4H)-one'>J41</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]], [[7kcf\|7kcf]], [[7kda\|7kda]], [[7kdb\|7kdb]]</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=7kce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kce OCA], [https://pdbe.org/7kce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kce RCSB], [https://www.ebi.ac.uk/pdbsum/7kce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kce 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 ==
		+	The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was recently implicated as a synthetic lethal target in cancers with deletion of the methylthioadenosine phosphorylase (MTAP) gene, which is adjacent to the CDKN2A tumor suppressor and codeleted with CDKN2A in approximately 15% of all cancers. Previous attempts to target MAT2A with small-molecule inhibitors identified cellular adaptations that blunted their efficacy. Here, we report the discovery of highly potent, selective, orally bioavailable MAT2A inhibitors that overcome these challenges. Fragment screening followed by iterative structure-guided design enabled >10000-fold improvement in potency of a family of allosteric MAT2A inhibitors that are substrate noncompetitive and inhibit release of the product, S-adenosyl methionine (SAM), from the enzyme's active site. We demonstrate that potent MAT2A inhibitors substantially reduce SAM levels in cancer cells and selectively block proliferation of MTAP-null cells both in tissue culture and xenograft tumors. These data supported progressing AG-270 into current clinical studies (ClinicalTrials.gov NCT03435250).
		+
		+	Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion.,Konteatis Z, Travins J, Gross S, Marjon K, Barnett A, Mandley E, Nicolay B, Nagaraja R, Chen Y, Sun Y, Liu Z, Yu J, Ye Z, Jiang F, Wei W, Fang C, Gao Y, Kalev P, Hyer ML, DeLaBarre B, Jin L, Padyana AK, Dang L, Murtie J, Biller SA, Sui Z, Marks KM J Med Chem. 2021 Apr 8. doi: 10.1021/acs.jmedchem.0c01895. PMID:33829783<ref>PMID:33829783</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kce" 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 A]]	+	[[Category: Jin, L]]
		+	[[Category: Padyana, A]]
		+	[[Category: Allosteric inhibitor]]
		+	[[Category: S-adenosylmethionine synthase isoform type-2]]
		+	[[Category: Sam]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-inhibitor complex]]

OCA at 08:23, 21 April 2021

OCA — Wed, 21 Apr 2021 08:23:46 GMT

←Older revision		Revision as of 08:23, 21 April 2021
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-	'''Unreleased structure'''

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

OCA at 09:19, 31 March 2021

OCA — Wed, 31 Mar 2021 09:19:35 GMT

←Older revision		Revision as of 09:19, 31 March 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

OCA at 05:27, 24 March 2021

OCA — Wed, 24 Mar 2021 05:27:19 GMT

←Older revision		Revision as of 05:27, 24 March 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

OCA at 06:50, 21 October 2020

OCA — Wed, 21 Oct 2020 06:50:44 GMT

←Older revision		Revision as of 06:50, 21 October 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 14 Oct 2020 04:23:24 GMT

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

←Older revision

Revision as of 04:23, 14 October 2020

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

OCA — Wed, 14 Oct 2020 04:23:23 GMT

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

New page

'''Unreleased structure'''

The entry 7kce is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]