8p4h: Difference between revisions
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==Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric compound IDEAYA cmpd A== | |||
<StructureSection load='8p4h' size='340' side='right'caption='[[8p4h]], [[Resolution|resolution]] 1.71Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8p4h]] is a 4 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=8P4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P4H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.71Å</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=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=UM6:7-chloranyl-4-[(3R)-3-fluoranylpyrrolidin-1-yl]-1-phenyl-quinazolin-2-one'>UM6</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=8p4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p4h OCA], [https://pdbe.org/8p4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p4h RCSB], [https://www.ebi.ac.uk/pdbsum/8p4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p4h ProSAT]</span></td></tr> | |||
</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 == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8p4h" style="background-color:#fffaf0;"></div> | ||
[[Category: Neumann | == References == | ||
[[Category: Thomsen | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Neumann L]] | |||
[[Category: Thieulin-Pardo G]] | |||
[[Category: Thomsen M]] | |||
