9RT8

Crystal structure of Cryptosporidium parvum Thioredoxin Reductase in complex with Aurothiomalate

9RT8 の概要

• エントリーDOI: 10.2210/pdb9rt8/pdb
• 分子名称: Thioredoxin reductase, FLAVIN-ADENINE DINUCLEOTIDE, GOLD ION, ... (4 entities in total)
• 機能のキーワード: reductase, flavoprotein
• 由来する生物種: Cryptosporidium parvum
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 229131.71

構造登録者

Gabriele, F.,Palerma, M.,Ardini, M.,Bogard, J.,Ippoliti, R.,Williams, D.L.,Angelucci, F. (登録日: 2025-07-02, 公開日: 2026-06-03, 最終更新日: 2026-06-10)

主引用文献

Gabriele, F.,Palerma, M.,Bogard, J.,Paluzzi, L.,Zineddu, S.,Geri, A.,Vitali, V.,Massai, L.,Ardini, M.,Bellelli, A.,Petukhov, P.A.,Ippoliti, R.,Messori, L.,Williams, D.L.,Angelucci, F.
Gold-containing compounds target an apicomplexan Thioredoxin reductase: Disclosing reactivity through structural and functional characterization.
Int.J.Biol.Macromol., 369:152627-152627, 2026

PubMed Abstract: Cryptosporidium spp. cause cryptosporidiosis, a severe diarrheal disease, particularly in young children and immunocompromised individuals. Treatment options are limited, and the only approved drug, nitazoxanide, is poorly effective in the most susceptible populations. Cryptosporidium relies exclusively on the thioredoxin reductase/thioredoxin (TrxR/Trx) system for redox homeostasis as Cryptosporidium lacks a glutathione reductase gene. Consistent with this vulnerability, TrxR ablation blocks parasite proliferation and sexual development, identifying TrxR as an essential drug target. C. parvum TrxR (CpTrxR) contains two redox-active cysteine motifs: a conserved N-terminal site and an apicomplexan-specific C-terminal site absent in human TrxRs. Here, by employing six structurally diverse gold-containing compounds, including clinically used agents, we probed the reactivity of CpTrxR toward these pharmacologically relevant chemotypes. Through a combination of X-ray crystallography, mass spectrometry, and functional studies, we discovered that enzyme inhibition arises from the distinct chemical properties of these compounds, which enable them to target either the N-terminal or the apicomplexan-specific C-terminal redox sites. These findings reinforce the potential of CpTrxR as a chemically tractable and parasite-selective target and establish gold-based scaffolds as a promising foundation for developing novel anti-Cryptosporidium therapeutics.

PubMed: 42162589
DOI: 10.1016/j.ijbiomac.2026.152627

実験手法

X-RAY DIFFRACTION (2.3 Å)