5J9C

Crystal structure of peroxiredoxin Asp f3 C31S/C61S variant

5J9C の概要

• エントリーDOI: 10.2210/pdb5j9c/pdb
• 関連するPDBエントリー: 5J9B
• 分子名称: peroxiredoxin Asp f3, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: peroxiredoxin, aspergillus, oxidoreductase
• 由来する生物種: Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100)
• 細胞内の位置: Peroxisome : O43099
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38681.79

構造登録者

Bzymek, K.P.,Williams, J.C.,Hong, T.B.,Bagramyan, K.,Kalkum, M. (登録日: 2016-04-08, 公開日: 2016-09-21, 最終更新日: 2023-09-27)

主引用文献

Hillmann, F.,Bagramyan, K.,Straburger, M.,Heinekamp, T.,Hong, T.B.,Bzymek, K.P.,Williams, J.C.,Brakhage, A.A.,Kalkum, M.
The Crystal Structure of Peroxiredoxin Asp f3 Provides Mechanistic Insight into Oxidative Stress Resistance and Virulence of Aspergillus fumigatus.
Sci Rep, 6:33396-33396, 2016

PubMed Abstract: Invasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin. The latter exhibits a thioredoxin fold and a homodimeric structure with two intermolecular disulfide bonds in its oxidized state. Replacement of the Asp f3 cysteines with serine residues retained its dimeric structure, but diminished Asp f3's peroxidase activity, and extended the alpha-helix with the former peroxidatic cysteine residue C61 by six residues. The asp f3 deletion mutant was sensitive to ROS, and this phenotype was rescued by ectopic expression of Asp f3. Furthermore, we showed that deletion of asp f3 rendered A. fumigatus avirulent in a mouse model of pulmonary aspergillosis. The conserved expression of Asp f3 homologs in medically relevant molds and yeasts prompts future evaluation of Asp f3 as a potential therapeutic target.

PubMed: 27624005
DOI: 10.1038/srep33396

実験手法

X-RAY DIFFRACTION (1.956 Å)