7bht: Difference between revisions

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 <StructureSection load='7bht' size='340' side='right'caption='[[7bht]], [[Resolution|resolution]] 1.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7bht]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7bht]] 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=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT 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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=TO8:7-chloranyl-4-(dimethylamino)-1~{H}-quinazolin-2-one'>TO8</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]] 1.052&#8491;</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='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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=TO8:7-chloranyl-4-(dimethylamino)-1~{H}-quinazolin-2-one'>TO8</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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht 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.
+[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 ==
-MAT2a is a methionine adenosyltransferase that synthesizes the essential metabolite S-adenosylmethionine (SAM) from methionine and ATP. Tumors bearing the co-deletion of p16 and MTAP genes have been shown to be sensitive to MAT2a inhibition, making it an attractive target for treatment of MTAP-deleted cancers. A fragment-based lead generation campaign identified weak but efficient hits binding in a known allosteric site. By use of structure-guided design and systematic SAR exploration, the hits were elaborated through a merging and growing strategy into an arylquinazolinone series of potent MAT2a inhibitors. The selected in vivo tool compound 28 reduced SAM-dependent methylation events in cells and inhibited proliferation of MTAP-null cells in vitro. In vivo studies showed that 28 was able to induce antitumor response in an MTAP knockout HCT116 xenograft model.
-Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model.,De Fusco C, Schimpl M, Borjesson U, Cheung T, Collie I, Evans L, Narasimhan P, Stubbs C, Vazquez-Chantada M, Wagner DJ, Grondine M, Sanders MG, Tentarelli S, Underwood E, Argyrou A, Smith JM, Lynch JT, Chiarparin E, Robb G, Bagal SK, Scott JS J Med Chem. 2021 Apr 26. doi: 10.1021/acs.jmedchem.1c00067. PMID:33900758<ref>PMID:33900758</ref>
+==See Also==
+*[[S-adenosylmethionine synthetase 3D structures|S-adenosylmethionine synthetase 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 7bht" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Methionine adenosyltransferase]]
+[[Category: Argyrou A]]
-[[Category: Argyrou, A]]
+[[Category: Bagal S]]
-[[Category: Bagal, S]]
+[[Category: Borjesson U]]
-[[Category: Borjesson, U]]
+[[Category: Cheung T]]
-[[Category: Cheung, T]]
+[[Category: Chiarparin E]]
-[[Category: Chiarparin, E]]
+[[Category: Collie I]]
-[[Category: Collie, I]]
+[[Category: De Fusco C]]
-[[Category: Evans, L]]
+[[Category: Evans L]]
-[[Category: Fusco, C De]]
+[[Category: Grondine M]]
-[[Category: Grondine, M]]
+[[Category: Narasimhan P]]
-[[Category: Narasimhan, P]]
+[[Category: Robb G]]
-[[Category: Robb, G]]
+[[Category: Schimpl M]]
-[[Category: Schimpl, M]]
+[[Category: Scott JS]]
-[[Category: Scott, J S]]
+[[Category: Stubbs C]]
-[[Category: Stubbs, C]]
+[[Category: Tentarelli S]]
-[[Category: Tentarelli, S]]
+[[Category: Underwood E]]
-[[Category: Underwood, E]]
+[[Category: Vazquez-Chantada M]]
-[[Category: Vazquez-Chantada, M]]
+[[Category: Wagner DJ]]
-[[Category: Wagner, D J]]
-[[Category: Allosteric inhibitor]]
-[[Category: Fragment-based drug design]]
-[[Category: Oncology]]
-[[Category: Synthetic lethal therapy]]
-[[Category: Transferase]]