Structure of the Trehalose-6-phosphate Phosphatase from Reveals Key Design Principles for Anthelmintic Drugs

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Here, we describe the structure of trehalose-6-phosphate phosphatase (T6PP) from Brugia malayi. This enzyme is essential to the organism; deletion of the gene encoding T6PP results in toxic accumulation of trehalose 6-phosphate. Structure-guided mutagenesis coupled with kinetic analyses revealed residues important for binding and catalysis. The model for substrate binding suggests a binding mode in which shape complementarity plays a major role. Conservation of binding residues among T6PP orthologs present in pathogenic nematodes and bacteria favors T6PP as a suitable target for broad-range anthelmintic and antibacterial drug design.

Vyšlo v časopise: Structure of the Trehalose-6-phosphate Phosphatase from Reveals Key Design Principles for Anthelmintic Drugs. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004245
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004245

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