Loading
PDBj
メニューPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

7EHJ

human MTHFD2 in complex with compound 21, cofactor and phosphate.

7EHJ の概要
エントリーDOI10.2210/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
Lee, L.C.,Peng, Y.H.,Wu, S.Y. (登録日: 2021-03-29, 公開日: 2021-08-11, 最終更新日: 2023-11-29)
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: 34337952
DOI: 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)
構造検証レポート
Validation report summary of 7ehj
検証レポート(詳細版)ダウンロードをダウンロード

227344

件を2024-11-13に公開中

PDB statisticsPDBj update infoContact PDBjnumon