6HN3

wildtype form (apo) of human GPX4 with Se-Cys46

6HN3 の概要

• エントリーDOI: 10.2210/pdb6hn3/pdb
• 関連するPDBエントリー: 6HKQ
• 分子名称: Phospholipid hydroperoxide glutathione peroxidase, CHLORIDE ION, ETHANOL, ... (5 entities in total)
• 機能のキーワード: anti-oxidatve defense system, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20637.43

構造登録者

Hillig, R.C.,Moosmayer, D.,Hilpmann, A.,Hoffmann, J.,Schnirch, L.,Eaton, J.K.,Badock, V.,Gradl, S. (登録日: 2018-09-13, 公開日: 2020-04-01, 最終更新日: 2024-01-24)

主引用文献

Moosmayer, D.,Hilpmann, A.,Hoffmann, J.,Schnirch, L.,Zimmermann, K.,Badock, V.,Furst, L.,Eaton, J.K.,Viswanathan, V.S.,Schreiber, S.L.,Gradl, S.,Hillig, R.C.
Crystal structures of the selenoprotein glutathione peroxidase 4 in its apo form and in complex with the covalently bound inhibitor ML162.
Acta Crystallogr D Struct Biol, 77:237-248, 2021

PubMed Abstract: Wild-type human glutathione peroxidase 4 (GPX4) was co-expressed with SBP2 (selenocysteine insertion sequence-binding protein 2) in human HEK cells to achieve efficient production of this selenocysteine-containing enzyme on a preparative scale for structural biology. The protein was purified and crystallized, and the crystal structure of the wild-type form of GPX4 was determined at 1.0 Å resolution. The overall fold and the active site are conserved compared with previously determined crystal structures of mutated forms of GPX4. A mass-spectrometry-based approach was developed to monitor the reaction of the active-site selenocysteine Sec46 with covalent inhibitors. This, together with the introduction of a surface mutant (Cys66Ser), enabled the crystal structure determination of GPX4 in complex with the covalent inhibitor ML162 [(S)-enantiomer]. The mass-spectrometry-based approach described here opens the path to further co-complex crystal structures of this potential cancer drug target in complex with covalent inhibitors.

PubMed: 33559612
DOI: 10.1107/S2059798320016125

実験手法

X-RAY DIFFRACTION (1.01 Å)