7TOF

Structure of G6PD-WT dimer with no symmetry applied

7TOF の概要

• エントリーDOI: 10.2210/pdb7tof/pdb
• EMDBエントリー: 26031
• 分子名称: Glucose-6-phosphate 1-dehydrogenase (1 entity in total)
• 機能のキーワード: apo protein, 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: 118665.17

構造登録者

Wei, X.,Marmorstein, R. (登録日: 2022-01-24, 公開日: 2022-09-14, 最終更新日: 2025-06-04)

主引用文献

Wei, X.,Kixmoeller, K.,Baltrusaitis, E.,Yang, X.,Marmorstein, R.
Allosteric role of a structural NADP + molecule in glucose-6-phosphate dehydrogenase activity.
Proc.Natl.Acad.Sci.USA, 119:e2119695119-e2119695119, 2022

PubMed Abstract: Human glucose-6-phosphate dehydrogenase (G6PD) is the main cellular source of NADPH, and thus plays a key role in maintaining reduced glutathione to protect cells from oxidative stress disorders such as hemolytic anemia. G6PD is a multimeric enzyme that uses the cofactors β-D-glucose 6-phosphate (G6P) and "catalytic" NADP (NADPc), as well as a "structural" NADP (NADPs) located ∼25 Å from the active site, to generate NADPH. While X-ray crystallographic and biochemical studies have revealed a role for NADPs in maintaining the catalytic activity by stabilizing the multimeric G6PD conformation, other potential roles for NADPs have not been evaluated. Here, we determined the high resolution cryo-electron microscopy structures of human wild-type G6PD in the absence of bound ligands and a catalytic G6PD-D200N mutant bound to NADPc and NADPs in the absence or presence of G6P. A comparison of these structures, together with previously reported structures, reveals that the unliganded human G6PD forms a mixture of dimers and tetramers with similar overall folds, and binding of NADPs induces a structural ordering of a C-terminal extension region and allosterically regulates G6P binding and catalysis. These studies have implications for understanding G6PD deficiencies and for therapy of G6PD-mediated disorders.

PubMed: 35858355
DOI: 10.1073/pnas.2119695119

実験手法

ELECTRON MICROSCOPY (3.7 Å)