| Inhibition of the ecto-ATPdiphosphohydrolase of Schistosoma mansoni by thapsigargin. | |
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MedLine Citation:
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PMID: 11332599 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S M Martins; C R Torres; S T Ferreira |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Bioscience reports Volume: 20 ISSN: 0144-8463 ISO Abbreviation: Biosci. Rep. Publication Date: 2000 Oct |
Date Detail:
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Created Date: 2001-05-02 Completed Date: 2001-09-20 Revised Date: 2008-09-14 |
Medline Journal Info:
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Nlm Unique ID: 8102797 Medline TA: Biosci Rep Country: United States |
Other Details:
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Languages: eng Pagination: 369-81 Citation Subset: IM |
Affiliation:
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Departamento de Bioquímica Médica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Diphosphate
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metabolism Adenosine Triphosphate / metabolism Animals Antigens, CD Apyrase / antagonists & inhibitors*, metabolism* Calcium / metabolism Calcium-Transporting ATPases / antagonists & inhibitors, metabolism Enzyme Inhibitors / pharmacology* Hydrolysis Magnesium / metabolism Plant Extracts / pharmacology Sarcoplasmic Reticulum Calcium-Transporting ATPases Schistosoma mansoni / drug effects*, enzymology* Thapsigargin / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Enzyme Inhibitors; 0/Plant Extracts; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate; 67526-95-8/Thapsigargin; 7439-95-4/Magnesium; 7440-70-2/Calcium; EC 3.6.1.5/Apyrase; EC 3.6.1.5/CD39 antigen; EC 3.6.1.8/Calcium-Transporting ATPases; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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