2WGR

Combining crystallography and molecular dynamics: The case of Schistosoma mansoni phospholipid glutathione peroxidase

2WGR の概要

• エントリーDOI: 10.2210/pdb2wgr/pdb
• 関連するPDBエントリー: 2V1M
• 分子名称: GLUTATHIONE PEROXIDASE, PYROPHOSPHATE 2- (3 entities in total)
• 機能のキーワード: selenium, oxidoreductase, selenocysteine, schistosomiasis, lipid gsh peroxidase, molecular dynamics simulations, ros detoxification pathway
• 由来する生物種: SCHISTOSOMA MANSONI
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19613.15

構造登録者

Dimastrogiovanni, D.,Anselmi, M.,Miele, A.E.,Boumis, G.,Angelucci, F.,Di Nola, A.,Brunori, M.,Bellelli, A. (登録日: 2009-04-24, 公開日: 2009-09-08, 最終更新日: 2023-12-13)

主引用文献

Dimastrogiovanni, D.,Anselmi, M.,Miele, A.E.,Boumis, G.,Petersson, L.,Angelucci, F.,Nola, A.D.,Brunori, M.,Bellelli, A.
Combining Crystallography and Molecular Dynamics: The Case of Schistosoma Mansoni Phospholipid Glutathione Peroxidase.
Proteins, 78:259-, 2010

PubMed Abstract: Oxidative stress is a widespread challenge for living organisms, and especially so for parasitic ones, given the fact that their hosts can produce reactive oxygen species (ROS) as a mechanism of defense. Thus, long lived parasites, such as the flatworm Schistosomes, have evolved refined enzymatic systems capable of detoxifying ROS. Among these, glutathione peroxidases (Gpx) are a family of sulfur or selenium-dependent isozymes sharing the ability to reduce peroxides using the reducing equivalents provided by glutathione or possibly small proteins such as thioredoxin. As for other frontline antioxidant enzymatic systems, Gpxs are localized in the tegument of the Schistosomes, the outermost defense layer. In this article, we present the first crystal structure at 1.0 and 1.7 A resolution of two recombinant SmGpxs, carrying the active site mutations Sec43Cys and Sec43Ser, respectively. The structures confirm that this enzyme belongs to the monomeric class 4 (phospholipid hydroperoxide) Gpx. In the case of the Sec to Cys mutant, the catalytic Cys residue is oxidized to sulfonic acid. By combining static crystallography with molecular dynamics simulations, we obtained insight into the substrate binding sites and the conformational changes relevant to catalysis, proposing a role for the unusual reactivity of the catalytic residue.

PubMed: 19714775
DOI: 10.1002/PROT.22536

実験手法

X-RAY DIFFRACTION (1.7 Å)