7EHJ
human MTHFD2 in complex with compound 21, cofactor and phosphate.
7EHJ の概要
エントリーDOI | 10.2210/pdb7ehj/pdb |
関連するPDBエントリー | 7EHM 7EHN 7EHV |
分子名称 | Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial, (2S)-2-[[4-[(4-azanyl-6-oxidanyl-pyrimidin-5-yl)carbamoylamino]phenyl]carbonylamino]pentanedioic acid, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total) |
機能のキーワード | mthfd2, methylenetetrahydrofolate dehydrogenase 2, 1c metabolism, mitocondria, oxidoreductase |
由来する生物種 | Homo sapiens (Human) |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 70720.62 |
構造登録者 | |
主引用文献 | Lee, L.C.,Peng, Y.H.,Chang, H.H.,Hsu, T.,Lu, C.T.,Huang, C.H.,Hsueh, C.C.,Kung, F.C.,Kuo, C.C.,Jiaang, W.T.,Wu, S.Y. Xanthine Derivatives Reveal an Allosteric Binding Site in Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2). J.Med.Chem., 64:11288-11301, 2021 Cited by PubMed Abstract: 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 , which allosterically binds to MTHFD2 and coexists with the substrate analogue. A kinetic study demonstrated the uncompetitive inhibition of MTHFD2 by . 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 , 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. PubMed: 34337952DOI: 10.1021/acs.jmedchem.1c00663 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.16 Å) |
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