Discovery of a small molecule allosteric activator of human thiosulfate sulfurtransferase


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    Recent studies showed that thiosulfate sulfurtransferase (TST) is one of the few peripherally expressed genes that has been identified as a genetic risk factor for metabolic health, with clear evidence of a negative correlation with the development of obesity-related type 2 diabetes with insulin resistance2,3. Thiosulfate, a substrate for TST, is administered to diabetic mice to improve their glucose intolerance and insulin resistance, in part by increasing secretion of the insulin-sensitizing hormone adiponectin from adipocytes3T3-L12–5. In addition, hTST and its substrate, thiosulfate, have beneficial effects on hyperglycemia induced kidney damage in zebrafish embryos6. Therefore, development of effective TST activators offers the possibility to create novel antidiabetic drugs and the identification of crystal structure of human TST will help to develop it. Although a high-resolution structure of the highly homologous bovine TST is available7,8, there exist subtle changes in the amino acid composition of residues peripheral to the predicted active site cysteine in human TST.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    • van Goor, Harry, Supervisor
    • Groves, Matthew, Supervisor
    Datum van toekenning11-jan.-2023
    Plaats van publicatie[Groningen]
    StatusPublished - 2023

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