9ro3

Crystal structure of Cryptosporidium parvum Thioredoxin Reductase in complex with the auranofin analogue AuP(OCH3)3Cl

spinqualitylabelsall models 9ro3, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ro3 is a 4 chain structure with sequence from Cryptosporidium parvum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: AU, FAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C8CCG0_CRYPV Publication Abstract from PubMed 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. Gold-containing compounds target an apicomplexan Thioredoxin reductase: Disclosing reactivity through structural and functional characterization.,Gabriele F, Palerma M, Bogard J, Paluzzi L, Zineddu S, Geri A, Vitali V, Massai L, Ardini M, Bellelli A, Petukhov PA, Ippoliti R, Messori L, Williams DL, Angelucci F Int J Biol Macromol. 2026 May 19;369:152627. doi: 10.1016/j.ijbiomac.2026.152627. PMID:42162589 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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