6E07

Crystal structure of Canton G6PD in complex with structural NADP

「5VG5」から置き換えられました

6E07 の概要

• エントリーDOI: 10.2210/pdb6e07/pdb
• 分子名称: Glucose-6-phosphate 1-dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: g6pd, nadp, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 483686.11

構造登録者

Rahighi, S.,Mochly-Rosen, D.,Wakatsuki, S. (登録日: 2018-07-06, 公開日: 2018-07-25, 最終更新日: 2023-10-11)

主引用文献

Hwang, S.,Mruk, K.,Rahighi, S.,Raub, A.G.,Chen, C.H.,Dorn, L.E.,Horikoshi, N.,Wakatsuki, S.,Chen, J.K.,Mochly-Rosen, D.
Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator.
Nat Commun, 9:4045-4045, 2018

PubMed Abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the Canton mutant and several other common G6PD mutants. AG1 reduces oxidative stress in cells and zebrafish. Furthermore, AG1 decreases chloroquine- or diamide-induced oxidative stress in human erythrocytes. Our study suggests that a pharmacological agent, of which AG1 may be a lead, will likely alleviate the challenges associated with G6PD deficiency.

PubMed: 30279493
DOI: 10.1038/s41467-018-06447-z

実験手法

X-RAY DIFFRACTION (2.6 Å)