ArticleMolecular and biochemical parasitology2009
Cross-species activation of trypanosome S-adenosylmethionine decarboxylase by the regulatory subunit prozyme.
Article in Molecular and biochemical parasitology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- The Role of Spermidine and Its Key Metabolites in Important, Pathogenic Human Viruses and in Parasitic Infections Caused byBiomolecules · 2023Review
- Structure-Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines againstPharmaceutics · 2023Article
- Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections.Frontiers in pharmacology · 2023Article
- Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022Review
- Polyamines in protozoan pathogens.The Journal of biological chemistry · 2018Review
- The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids.Pathogens (Basel, Switzerland) · 2018Review
- The Major Protein Arginine Methyltransferase inThe Journal of biological chemistry · 2017Article
- Arginase Is Essential for Survival of Leishmania donovani Promastigotes but Not Intracellular Amastigotes.Infection and immunity · 2017Article
- The Trypanosoma cruzi Diamine Transporter Is Essential for Robust Infection of Mammalian Cells.PloS one · 2016Article
- Product feedback regulation implicated in translational control of the Trypanosoma brucei S-adenosylmethionine decarboxylase regulatory subunit prozyme.Molecular microbiology · 2013Article
- Trypanosoma brucei S-adenosylmethionine decarboxylase N terminus is essential for allosteric activation by the regulatory subunit prozyme.The Journal of biological chemistry · 2013Article
- Characterization of a Novel Putative S-Adenosylmethionine Decarboxylase-Like Protein from Leishmania donovani.PloS one · 2013Article
- Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities.The Biochemical journal · 2011Review
- Current status of the polyamine research field.Methods in molecular biology (Clifton, N.J.) · 2011Review
- A high-affinity putrescine-cadaverine transporter from Trypanosoma cruzi.Molecular microbiology · 2010Article
- Structural biology of S-adenosylmethionine decarboxylase.Amino acids · 2010Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease (American trypanosomiasis), a neglected disease of Central and South America. Polyamines are small organic cations that are required for cell growth and their biosynthesis has been the target of drug discovery efforts in both T. cruzi and the related Trypanosoma brucei parasites. Here we show that, as previously demonstrated for T. brucei, S-adenosylmethionine decarboxylase (AdoMetDC) from T. cruzi forms a heterodimer with prozyme, an inactive homolog that arose by gene duplication of the canonical enzyme uniquely in the trypanosomatids. The T. cruzi AdoMetDC/prozyme heterodimer is 110-fold more active than homodimeric AdoMetDC. Unlike for T. brucei AdoMetDC, the activity of the T. cruzi heterodimer is further stimulated by putrescine to generate an enzyme with similar catalytic efficiency to the fully activated T. brucei enzyme. The effects of prozyme on T. cruzi AdoMetDC are mediated by an increase in k(cat), while the predominant effect of putrescine is to lower the K(m). Finally we demonstrate that the cross-species heterodimers of T. cruzi and T. brucei AdoMetDC and prozyme pairs are functional, and that putrescine is required for prozyme to fully activate the mixed species heterodimers. These data demonstrate that prozyme mediated activation of AdoMetDC is a common mechanism required to regulate AdoMetDC activity in the trypanosomatids.
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