8p1v

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Current revision (09:17, 30 August 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8p1v is ON HOLD until Paper Publication
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==Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric compound 2==
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<StructureSection load='8p1v' size='340' side='right'caption='[[8p1v]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8p1v]] 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=8P1V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P1V FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.54&#8491;</td></tr>
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<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>, <scene name='pdbligand=WIV:6-cyclopropyl-~{N}-(2-methylindazol-5-yl)-1-propan-2-yl-pyrazolo[3,4-b]pyridine-4-carboxamide'>WIV</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8p1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p1v OCA], [https://pdbe.org/8p1v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p1v RCSB], [https://www.ebi.ac.uk/pdbsum/8p1v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p1v ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Methionine adenosyltransferase 2A (MAT2A) has been indicated as a drug target for oncology indications. Clinical trials with MAT2A inhibitors are currently on-going. Here, a structure-based virtual screening campaign was performed on the commercially available chemical space which yielded two novel MAT2A-inhibitor chemical series. The binding modes of the compounds were confirmed with X-ray crystallography. Both series have acceptable physicochemical properties and show nanomolar activity in the biochemical MAT2A inhibition assay and single-digit micromolar activity in the proliferation assay (MTAP -/- cell line). The identified compounds and the relating structural data could be helpful in related drug discovery projects.
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Authors: Thomsen, M., Thieulin-Pardo, G., Neumann, L.
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Discovery of novel methionine adenosyltransferase 2A (MAT2A) allosteric inhibitors by structure-based virtual screening.,Kalliokoski T, Kettunen H, Kumpulainen E, Kettunen E, Thieulin-Pardo G, Neumann L, Thomsen M, Paul R, Malyutina A, Georgiadou M Bioorg Med Chem Lett. 2023 Aug 15;94:129450. doi: 10.1016/j.bmcl.2023.129450. PMID:37591318<ref>PMID:37591318</ref>
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Description: Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric compound 2
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Thieulin-Pardo, G]]
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<div class="pdbe-citations 8p1v" style="background-color:#fffaf0;"></div>
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[[Category: Neumann, L]]
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== References ==
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[[Category: Thomsen, M]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Neumann L]]
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[[Category: Thieulin-Pardo G]]
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[[Category: Thomsen M]]

Current revision

Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric compound 2

PDB ID 8p1v

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