ArticleEukaryotic cell2014
Inhibition and structure of Toxoplasma gondii purine nucleoside phosphorylase.
Article in Eukaryotic cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Discovery of potent anti-toxoplasmosis drugs from secondary metabolites in Citrus limon (lemon) leaves, supported in-silico study.Scientific reports · 2025Article
- Phosphate Binding in PNP Alters Transition-State Analogue Affinity and Subunit Cooperativity.Biochemistry · 2023Article
- Nanoformulation-Based 1,2,3-Triazole Sulfonamides for Anti-Tropical medicine and infectious disease · 2023Article
- Intranasal immunisation with recombinant Toxoplasma gondii uridine phosphorylase confers resistance against acute toxoplasmosis in mice.Parasite (Paris, France) · 2023Article
- New Nucleic Base-Tethered Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Compounds: Synthesis and Antiparasitic Activity.Molecules (Basel, Switzerland) · 2022Article
- Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds againstPharmaceutics · 2022Article
- Synthesis and anti-Annals of medicine and surgery (2012) · 2022Article
- Strained Conformations of Nucleosides in Active Sites of Nucleoside Phosphorylases.Biomolecules · 2020Review
- Synthesis and biological evaluation of ursolic acid derivatives bearing triazole moieties as potential anti-Toxoplasma gondii agents.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines.Molecules (Basel, Switzerland) · 2019Article
- Nucleoside Hydrolase NH 36: A Vital Enzyme for theFrontiers in immunology · 2019Review
- Twenty-six circulating antigens and two novel diagnostic candidate molecules identified in the serum of canines with experimental acute toxoplasmosis.Parasites & vectors · 2016Article
- Comparative genomics reveals Cyclospora cayetanensis possesses coccidia-like metabolism and invasion components but unique surface antigens.BMC genomics · 2016Article
- Immucillins ImmA and ImmH Are Effective and Non-toxic in the Treatment of Experimental Visceral Leishmaniasis.PLoS neglected tropical diseases · 2015Article
- Immucillins Impair Leishmania (L.) infantum chagasi and Leishmania (L.) amazonensis Multiplication In Vitro.PloS one · 2015Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The intracellular pathogen Toxoplasma gondii is a purine auxotroph that relies on purine salvage for proliferation. We have optimized T. gondii purine nucleoside phosphorylase (TgPNP) stability and crystallized TgPNP with phosphate and immucillin-H, a transition-state analogue that has high affinity for the enzyme. Immucillin-H bound to TgPNP with a dissociation constant of 370 pM, the highest affinity of 11 immucillins selected to probe the catalytic site. The specificity for transition-state analogues indicated an early dissociative transition state for TgPNP. Compared to Plasmodium falciparum PNP, large substituents surrounding the 5'-hydroxyl group of inhibitors demonstrate reduced capacity for TgPNP inhibition. Catalytic discrimination against large 5' groups is consistent with the inability of TgPNP to catalyze the phosphorolysis of 5'-methylthioinosine to hypoxanthine. In contrast to mammalian PNP, the 2'-hydroxyl group is crucial for inhibitor binding in the catalytic site of TgPNP. This first crystal structure of TgPNP describes the basis for discrimination against 5'-methylthioinosine and similarly 5'-hydroxy-substituted immucillins; structural differences reflect the unique adaptations of purine salvage pathways of Apicomplexa.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.