View source for 6jib


==Human MTHFD2 in complex with DS44960156==
<StructureSection load='6jib' size='340' side='right'caption='[[6jib]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jib]] 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=6JIB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JIB 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]] 2.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BQF:4-(5-oxo-1,5-dihydro-2H-[1]benzopyrano[3,4-c]pyridine-3(4H)-carbonyl)benzoic+acid'>BQF</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=6jib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jib OCA], [https://pdbe.org/6jib PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jib RCSB], [https://www.ebi.ac.uk/pdbsum/6jib PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jib ProSAT]</span></td></tr>
</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 (&gt;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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jib" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kawai J]]
[[Category: Matsui Y]]
[[Category: Suzuki M]]