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• W1893033718 endingPage "381" @default.
• W1893033718 startingPage "369" @default.
• W1893033718 abstract "ATPdiphosphohydrolases (ATPDases) are ubiquitous enzymes capable of hydrolyzing nucleoside di- and triphosphates. Although a number of possible physiological roles have been proposed for ATPDases, detailed studies on structure-function relationships have generally been hampered by the lack of specific inhibitors of these enzymes. We have previously characterized a Ca2+-activated ATPDase on the external surface of the tegument of Schistosoma mansoni, the etiologic agent of human schistosomiasis. In the present work, we have examined the effects of thapsigargin, a sesquiterpene lactone known as a high affinity inhibitor of sarco-endoplasmic reticulum calcium transport (SERCA) ATPase, on ATPDase activity. Whereas other lactones tested had little or no inhibitory action, thapsigargin inhibited ATP hydrolysis by the ATPDase (K(i) approximately 20 microM). Interestingly, hydrolysis of ADP was not inhibited by thapsigargin. The lack of inhibition of ATPase activity by orthovanadate, a specific inhibitor of P-type ATPases, and the inhibition of the Mg2+-stimulated ATP hydrolysis by thapsigargin ruled out the possibility that the observed inhibition of the ATPDase by thapsigargin could be due to the presence of contaminating SERCA ATPases in our preparation. Kinetic analysis indicated that a single active site in the ATPDase is responsible for hydrolysis of both ATP and ADP. Thapsigargin caused changes in both Vmax and Km for ATP, indicating a mixed type of inhibition. Inhibition by thapsigargin was little or not affected by changes in free Ca2+ or Mg2+ concentrations. These results suggest that interaction of thapsigargin with the S. mansoni ATPDase prevents binding of ATP or its hydrolysis at the active site, while ADP can still undergo catalysis." @default.
• W1893033718 created "2016-06-24" @default.
• W1893033718 creator A5070851422 @default.
• W1893033718 creator A5071839868 @default.
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• W1893033718 date "2000-10-01" @default.
• W1893033718 modified "2023-09-24" @default.
• W1893033718 title "Inhibition of the Ecto-ATPdiphosphohydrolase of Schistosoma mansoni by Thapsigargin" @default.
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• W1893033718 doi "https://doi.org/10.1023/a:1010330017583" @default.
• W1893033718 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11332599" @default.
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