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The Toxoplasma glucan phosphatase TgLaforin utilizes a distinct functional mechanism that can be exploited by therapeutic inhibitors

J Biol Chem. 2022-05; 
Robert D Murphy, Tiantian Chen, Jianping Lin, Rongjun He, Li Wu, Caden R Pearson, Savita Sharma, Carl D Vander Kooi, Anthony P Sinai, Zhong-Yin Zhang, Craig W Vander Kooi, Matthew S Gentry
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摘要

Toxoplasma gondii is an intracellular parasite that generates amylopectin granules (AGs), a polysaccharide associated with bradyzoites that define chronic T. gondii infection. AGs are postulated to act as an essential energy storage molecule that enable bradyzoite persistence, transmission, and reactivation. Importantly, reactivation can result in the life-threatening symptoms of toxoplasmosis. T. gondii encodes glucan dikinase and glucan phosphatase enzymes that are homologous to the plant and animal enzymes involved in reversible glucan phosphorylation and which are required for efficient polysaccharide degradation and utilization. However, the structural determinants that regulate reversible glucan phospho... More

关键词

AlphaFold2, Toxoplasma gondii, amylopectin, carbohydrate-binding protein, differential scanning fluorimetry, glucan phosphatase, hydrogen exchange mass spectrometry, laforin, phosphatase, size-exclusion chromatography with multiangle light scattering