7ehv
From Proteopedia
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==Human MTHFD2 in complex with compound 21 and 3== | ==Human MTHFD2 in complex with compound 21 and 3== | ||
| - | <StructureSection load='7ehv' size='340' side='right'caption='[[7ehv]]' scene=''> | + | <StructureSection load='7ehv' size='340' side='right'caption='[[7ehv]], [[Resolution|resolution]] 2.61Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EHV FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EHV FirstGlance]. <br> | ||
| - | </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=7ehv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ehv OCA], [https://pdbe.org/7ehv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ehv RCSB], [https://www.ebi.ac.uk/pdbsum/7ehv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ehv ProSAT]</span></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]] 2.61Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J49:(2S)-2-[[4-[(4-azanyl-6-oxidanyl-pyrimidin-5-yl)carbamoylamino]phenyl]carbonylamino]pentanedioic+acid'>J49</scene>, <scene name='pdbligand=J4L:1-(3,4-dichlorobenzyl)-8-(((1R,4R)-4-hydroxycyclohexyl)amino)-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione'>J4L</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=7ehv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ehv OCA], [https://pdbe.org/7ehv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ehv RCSB], [https://www.ebi.ac.uk/pdbsum/7ehv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ehv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays an important role in one-carbon metabolism. The MTHFD2 gene is upregulated in various cancers but very low or undetectable in normal proliferating cells, and therefore a potential target for cancer treatment. In this study, we present the structure of MTHFD2 in complex with xanthine derivative 15, which allosterically binds to MTHFD2 and coexists with the substrate analogue. A kinetic study demonstrated the uncompetitive inhibition of MTHFD2 by 15. Allosteric inhibitors often provide good selectivity and, indeed, xanthine derivatives are highly selective for MTHFD2. Moreover, several conformational changes were observed upon the binding of 15, which impeded the binding of the cofactor and phosphate to MTHFD2. To the best of our knowledge, this is the first study to identify allosteric inhibitors targeting the MTHFD family and our results would provide insights on the inhibition mechanism of MTHFD proteins and the development of novel inhibitors. | ||
| + | |||
| + | Xanthine Derivatives Reveal an Allosteric Binding Site in Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2).,Lee LC, Peng YH, Chang HH, Hsu T, Lu CT, Huang CH, Hsueh CC, Kung FC, Kuo CC, Jiaang WT, Wu SY J Med Chem. 2021 Aug 2. doi: 10.1021/acs.jmedchem.1c00663. PMID:34337952<ref>PMID:34337952</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ehv" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Human MTHFD2 in complex with compound 21 and 3
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Categories: Large Structures | Lee LC | Peng YH | Wu SY
