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<StructureSection load='6jid' size='340' side='right'caption='[[6jid]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='6jid' size='340' side='right'caption='[[6jid]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6jid]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JID OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6jid]] is a 2 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=6JID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JID FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BQC:5-(4-oxo-2-phenyl-1,5,7,8-tetrahydropyrido[4,3-d]pyrimidine-6(4H)-carbonyl)-1,3-dihydro-2H-2lambda~6~,1-benzothiazole-2,2-dione'>BQC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.5Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BQC:5-(4-oxo-2-phenyl-1,5,7,8-tetrahydropyrido[4,3-d]pyrimidine-6(4H)-carbonyl)-1,3-dihydro-2H-2lambda~6~,1-benzothiazole-2,2-dione'>BQC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6jid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jid OCA], [https://pdbe.org/6jid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jid RCSB], [https://www.ebi.ac.uk/pdbsum/6jid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jid ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/MTDC_HUMAN MTDC_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays a key role in one-carbon (1C) metabolism in human mitochondria, and its high expression correlates with poor survival of patients with various types of cancer. An isozyme-selective MTHFD2 inhibitor is highly attractive for potential use in cancer treatment. Herein, we disclose a novel isozyme-selective MTHFD2 inhibitor DS44960156, with a tricyclic coumarin scaffold, which was initially discovered via high-throughput screening (HTS) and improved using structure-based drug design (SBDD). DS44960156 would offer a good starting point for further optimization based on the following features: (1) unprecedented selectivity (>18-fold) for MTHFD2 over MTHFD1, (2) a molecular weight of less than 400, and (3) good ligand efficiency (LE). | |||
Structure-Based Design and Synthesis of an Isozyme-Selective MTHFD2 Inhibitor with a Tricyclic Coumarin Scaffold.,Kawai J, Ota M, Ohki H, Toki T, Suzuki M, Shimada T, Matsui S, Inoue H, Sugihara C, Matsuhashi N, Matsui Y, Takaishi S, Nakayama K ACS Med Chem Lett. 2019 May 24;10(6):893-898. doi:, 10.1021/acsmedchemlett.9b00069. eCollection 2019 Jun 13. PMID:31223444<ref>PMID:31223444</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6jid" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Kawai | [[Category: Kawai J]] | ||
[[Category: Matsuhashi | [[Category: Matsuhashi N]] | ||
[[Category: Matsui | [[Category: Matsui Y]] | ||
[[Category: Suzuki | [[Category: Suzuki M]] | ||
Latest revision as of 13:09, 22 November 2023
Human MTHFD2 in complex with Compound 1Human MTHFD2 in complex with Compound 1
Structural highlights
FunctionPublication Abstract from PubMedMethylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays a key role in one-carbon (1C) metabolism in human mitochondria, and its high expression correlates with poor survival of patients with various types of cancer. An isozyme-selective MTHFD2 inhibitor is highly attractive for potential use in cancer treatment. Herein, we disclose a novel isozyme-selective MTHFD2 inhibitor DS44960156, with a tricyclic coumarin scaffold, which was initially discovered via high-throughput screening (HTS) and improved using structure-based drug design (SBDD). DS44960156 would offer a good starting point for further optimization based on the following features: (1) unprecedented selectivity (>18-fold) for MTHFD2 over MTHFD1, (2) a molecular weight of less than 400, and (3) good ligand efficiency (LE). Structure-Based Design and Synthesis of an Isozyme-Selective MTHFD2 Inhibitor with a Tricyclic Coumarin Scaffold.,Kawai J, Ota M, Ohki H, Toki T, Suzuki M, Shimada T, Matsui S, Inoue H, Sugihara C, Matsuhashi N, Matsui Y, Takaishi S, Nakayama K ACS Med Chem Lett. 2019 May 24;10(6):893-898. doi:, 10.1021/acsmedchemlett.9b00069. eCollection 2019 Jun 13. PMID:31223444[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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