View source for 9rte


==Crystal structure of Cryptosporidium parvum Thioredoxin Reductase in complex with the dicarbene Au(I) complex Au(NHC)2PF6==
<StructureSection load='9rte' size='340' side='right'caption='[[9rte]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9rte]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_parvum Cryptosporidium parvum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9RTE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RTE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9rte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rte OCA], [https://pdbe.org/9rte PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rte RCSB], [https://www.ebi.ac.uk/pdbsum/9rte PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rte ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8IS93_CRYPV Q8IS93_CRYPV] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:42162589</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9rte" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cryptosporidium parvum]]
[[Category: Large Structures]]
[[Category: Angelucci F]]
[[Category: Ardini M]]
[[Category: Bogard J]]
[[Category: Gabriele F]]
[[Category: Ippoliti R]]
[[Category: Palerma M]]
[[Category: Williams DL]]