ArticleGlycobiology2010
Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase.
Article in Glycobiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Glycocalyx-Driven Immunomodulation in Trypanosoma cruzi: Structures, Host Responses, Diagnostic and Therapeutic Targeting.Parasite immunology · 2026Review
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- Consumption of Galactose byPathogens (Basel, Switzerland) · 2022Article
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- Nucleotide sugar biosynthesis occurs in the glycosomes of procyclic and bloodstream form Trypanosoma brucei.PLoS neglected tropical diseases · 2021Article
- Proteomic analysis of glycosomes from Trypanosoma cruzi epimastigotes.Molecular and biochemical parasitology · 2019Article
- Identification ofMolecules (Basel, Switzerland) · 2019Article
- Crystal structure and insights into the oligomeric state of UDP-glucose pyrophosphorylase from sugarcane.PloS one · 2018Article
- Depletion of UDP-Glucose and UDP-Galactose Using a Degron System Leads to Growth Cessation of Leishmania major.PLoS neglected tropical diseases · 2015Article
- A quaternary mechanism enables the complex biological functions of octameric human UDP-glucose pyrophosphorylase, a key enzyme in cell metabolism.Scientific reports · 2015Article
- Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.PLoS pathogens · 2015Article
- High-confidence glycosome proteome for procyclic form Trypanosoma brucei by epitope-tag organelle enrichment and SILAC proteomics.Journal of proteome research · 2014Article
- Genetic and structural validation of Aspergillus fumigatus N-acetylphosphoglucosamine mutase as an antifungal target.Bioscience reports · 2013Article
- Inhibition of nucleotide sugar transport in Trypanosoma brucei alters surface glycosylation.The Journal of biological chemistry · 2013Article
- Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase.Molecular microbiology · 2012Article
- Characterization, localization, essentiality, and high-resolution crystal structure of glucosamine 6-phosphate N-acetyltransferase from Trypanosoma brucei.Eukaryotic cell · 2011Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The protozoan parasite Trypanosoma brucei is the causative agent of the cattle disease Nagana and human African sleeping sickness. Glycoproteins play key roles in the parasite's survival and infectivity, and the de novo biosyntheses of the sugar nucleotides UDP-galactose (UDP-Gal), UDP-N-acetylglucosamine, and GDP-fucose have been shown to be essential for their growth. The only route to UDP-Gal in T. brucei is through the epimerization of UDP-glucose (UDP-Glc) by UDP-Glc 4'-epimerase. UDP-Glc is also the glucosyl donor for the unfolded glycoprotein glucosyltransferase (UGGT) involved in glycoprotein quality control in the endoplasmic reticulum and is the presumed donor for the synthesis of base J (β-D-glucosylhydroxymethyluracil), a rare deoxynucleotide found in telomere-proximal DNA in the bloodstream form of T. brucei. Considering that UDP-Glc plays such a central role in carbohydrate metabolism, we decided to characterize UDP-Glc biosynthesis in T. brucei. We identified and characterized the parasite UDP-glucose pyrophosphorylase (TbUGP), responsible for the formation of UDP-Glc from glucose-1-phosphate and UTP, and localized the enzyme to the peroxisome-like glycosome organelles of the parasite. Recombinant TbUGP was shown to be enzymatically active and specific for glucose-1-phosphate. The high-resolution crystal structure was also solved, providing a framework for the design of potential inhibitors against the parasite enzyme.
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