ArticleProceedings of the National Academy of Sciences of the United States of America2016
Structures of trehalose-6-phosphate phosphatase from pathogenic fungi reveal the mechanisms of substrate recognition and catalysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans.BMC microbiology · 2024Pooled it
- Article
- Accumulation of Trehalose 6-Phosphate in Candidozyma auris results in Decreased Echinocandin Resistance and Tolerance.Nature communications · 2025Article
- Article
- Non-catalytic and catalytic TREHALOSE-6-PHOSPHATE SYNTHASES interact with RAMOSA3 to control maize development.bioRxiv : the preprint server for biology · 2025Article
- Developing the trehalose biosynthesis pathway as an antifungal drug target.npj antimicrobials and resistance · 2025Review
- Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025Review
- Aloin remodels the cell wall of Candida albicans to reduce its hyphal virulence against oral candidiasis.Applied microbiology and biotechnology · 2025Article
- Antifungal and anti-biofilm effects of hydrazone derivatives onJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes.Chemical reviews · 2024Review
- Bioinformatic analyses to uncover genes involved in trehalose metabolism in the polyploid sugarcane.Scientific reports · 2022Article
- Fission yeast Duf89 and Duf8901 are cobalt/nickel-dependent phosphatase-pyrophosphatases that act via a covalent aspartyl-phosphate intermediate.The Journal of biological chemistry · 2022Article
- Recruitment of an ancient branching program to suppress carpel development in maize flowers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- In vitro characterization of Haemonchus contortus trehalose-6-phosphate phosphatase and its immunomodulatory effects on peripheral blood mononuclear cells (PBMCs).Parasites & vectors · 2021Article
- Role of Trehalose Synthesis in Ralstonia syzygii subsp. indonesiensis PW1001 in Inducing Hypersensitive Response on Eggplant (Solanum melongena cv. Senryo-nigou).The plant pathology journal · 2021Article
- Article
- Global Changes in AsexualMicroorganisms · 2021Article
- Green Synthesis of Silver Nanoparticles Using theACS omega · 2021Article
- Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis.Frontiers in cellular and infection microbiology · 2021Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Trehalose is a disaccharide essential for the survival and virulence of pathogenic fungi. The biosynthesis of trehalose requires trehalose-6-phosphate synthase, Tps1, and trehalose-6-phosphate phosphatase, Tps2. Here, we report the structures of the N-terminal domain of Tps2 (Tps2NTD) from Candida albicans, a transition-state complex of the Tps2 C-terminal trehalose-6-phosphate phosphatase domain (Tps2PD) bound to BeF3 and trehalose, and catalytically dead Tps2PD(D24N) from Cryptococcus neoformans bound to trehalose-6-phosphate (T6P). The Tps2NTD closely resembles the structure of Tps1 but lacks any catalytic activity. The Tps2PD-BeF3-trehalose and Tps2PD(D24N)-T6P complex structures reveal a "closed" conformation that is effected by extensive interactions between each trehalose hydroxyl group and residues of the cap and core domains of the protein, thereby providing exquisite substrate specificity. Disruption of any of the direct substrate-protein residue interactions leads to significant or complete loss of phosphatase activity. Notably, the Tps2PD-BeF3-trehalose complex structure captures an aspartyl-BeF3 covalent adduct, which closely mimics the proposed aspartyl-phosphate intermediate of the phosphatase catalytic cycle. Structures of substrate-free Tps2PD reveal an "open" conformation whereby the cap and core domains separate and visualize the striking conformational changes effected by substrate binding and product release and the role of two hinge regions centered at approximately residues 102-103 and 184-188. Significantly, tps2Δ, tps2NTDΔ, and tps2D705N strains are unable to grow at elevated temperatures. Combined, these studies provide a deeper understanding of the substrate recognition and catalytic mechanism of Tps2 and provide a structural basis for the future design of novel antifungal compounds against a target found in three major fungal pathogens.
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