7AOO

Plasmoredoxin, a redox-active protein unique for malaria parasites

7AOO の概要

• エントリーDOI: 10.2210/pdb7aoo/pdb
• 関連するPDBエントリー: 7AOJ
• 分子名称: Plasmoredoxin, GLYCEROL, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• 機能のキーワード: malaria, plasmodium falciparum, thioredoxin superfamily, redox metabolism, oxidoreductase
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 90253.24

構造登録者

Fritz-Wolf, K.,Bathke, J.,Rahlfs, S.,Becker, K. (登録日: 2020-10-14, 公開日: 2022-04-13, 最終更新日: 2024-06-19)

主引用文献

Fritz-Wolf, K.,Bathke, J.,Rahlfs, S.,Becker, K.
Crystal structure of plasmoredoxin, a redox-active protein unique for malaria parasites.
Curr Res Struct Biol, 4:87-95, 2022

PubMed Abstract: Plasmoredoxin is a 22 ​kDa thiol-disulfide oxidoreductase involved in cellular redox regulatory processes and antioxidant defense. The 1.6 ​Å structure of the protein, solved via X-ray crystallography, adopts a modified thioredoxin fold. The structure reveals that plasmoredoxin, unique for malarial parasites, forms a new subgroup of thioredoxin-like proteins together with tryparedoxin, unique for kinetoplastids. Unlike most members of this superfamily, Plrx does not have a proline residue within the CxxC redox motif. In addition, the Plrx structure has a distinct C-terminal domain. Similar to human thioredoxin, plasmoredoxin forms monomers and dimers, which are also structurally similar to the human thioredoxin dimer, and, as in humans, plasmoredoxin is inactive as a dimer. Monomer-dimer equilibrium depends on the surrounding redox conditions, which could support the parasite in reacting to oxidative challenges. Based on structural considerations, the residues of the dimer interface are likely to interact with target proteins. In contrast to and thioredoxin, however, there is a cluster of positively charged residues at the dimer interface of plasmoredoxin. These intersubunit (lysine) residues might allow binding of the protein to cellular membranes or to plasminogen. Malaria parasites lack catalase and glutathione peroxidase and therefore depend on their other glutathione and thioredoxin-dependent redox relays. Plasmoredoxin could be part of a so far unknown electron transfer system that only occurs in these parasites. Since the surface charge of plasmoredoxin differs significantly from other members of the thioredoxin superfamily, its three-dimensional structure can provide a model for designing selective redox-modulatory inhibitors.

PubMed: 35434650
DOI: 10.1016/j.crstbi.2022.03.004

実験手法

X-RAY DIFFRACTION (1.6 Å)