ArticleACS chemical biology2013
A novel allosteric inhibitor of the uridine diphosphate N-acetylglucosamine pyrophosphorylase from Trypanosoma brucei.
Article in ACS chemical biology, 2013. 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, 26 citations in OpenAlex.
- Article
- Nitrate assimilation compensates for cell wall biosynthesis in the absence ofApplied and environmental microbiology · 2024Article
- Article
- Nucleotide sugar biosynthesis occurs in the glycosomes of procyclic and bloodstream form Trypanosoma brucei.PLoS neglected tropical diseases · 2021Article
- A missense mutation in a patient with developmental delay affects the activity and structure of the hexosamine biosynthetic pathway enzyme AGX1.FEBS letters · 2021Article
- A mechanism-inspired UDP-RSC chemical biology · 2020Article
- Identification ofMolecules (Basel, Switzerland) · 2019Article
- UDP-Sugar Producing Pyrophosphorylases: Distinct and Essential Enzymes With Overlapping Substrate Specificities, ProvidingFrontiers in plant science · 2018Review
- Substrate Specificity and Inhibitor Sensitivity of Plant UDP-Sugar Producing Pyrophosphorylases.Frontiers in plant science · 2017Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Characterization of parasite-specific indels and their proposed relevance for selective anthelminthic drug targeting.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2016Article
- Transcriptomic profiling of host-parasite interactions in the microsporidian Trachipleistophora hominis.BMC genomics · 2015Article
- Depletion of M. tuberculosis GlmU from Infected Murine Lungs Effects the Clearance of the Pathogen.PLoS pathogens · 2015Article
- Fragment-Based De Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA.Angewandte Chemie (International ed. in English) · 2015Article
- Structure of uridine diphosphate N-acetylglucosamine pyrophosphorylase from Entamoeba histolytica.Acta crystallographica. Section F, Structural biology communications · 2015Article
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11 authors at 1 institution in 1 country.
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Abstract
Uridine diphosphate N-acetylglucosamine pyrophosphorylase (UAP) catalyzes the final reaction in the biosynthesis of UDP-GlcNAc, an essential metabolite in many organisms including Trypanosoma brucei, the etiological agent of Human African Trypanosomiasis. High-throughput screening of recombinant T. brucei UAP identified a UTP-competitive inhibitor with selectivity over the human counterpart despite the high level of conservation of active site residues. Biophysical characterization of the UAP enzyme kinetics revealed that the human and trypanosome enzymes both display a strictly ordered bi-bi mechanism, but with the order of substrate binding reversed. Structural characterization of the T. brucei UAP-inhibitor complex revealed that the inhibitor binds at an allosteric site absent in the human homologue that prevents the conformational rearrangement required to bind UTP. The identification of a selective inhibitory allosteric binding site in the parasite enzyme has therapeutic potential.
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