Tautomycin from the bacterium Streptomyces verticillatus. Another potent and specific inhibitor of protein phosphatases 1 and 2A.
Tautomycin inhibited the catalytic subunits of protein phosphatase-1 (Kiapp = 0.16 nM) more potently than protein phosphatase 2A (Kiapp = 0.4 nM), and the native forms of these enzymes in mammalian, protozoan and plant extracts were inhibited in a similar manner. Protein phosphatase 2B was inhibited 10,000-fold less potently, while two other phosphatases and six protein kinases were unaffected at 10 microM. Okadaic acid prevented the binding of tautomycin to protein phosphatase 2A, indicating a common binding site for both inhibitors. The different relative potencies of tautomycin and okadaic acid for protein phosphatases 1 and 2A suggest that parallel use of both inhibitors may help to identify physiological substrates for each enzyme.
MacKintosh
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Department of Biochemistry, University of Dundee, Scotland, UK.
Klumpp
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D000935:Antifungal Agents / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008387:Marine Toxins; D052998:Microcystins; D019319:Okadaic Acid; D010456:Peptides, Cyclic / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D006005:Phosphorylases / Q000378:metabolism; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D011714:Pyrans; D013141:Spiro Compounds; D013302:Streptomyces / Q000032:analysis*
D000935:Antifungal Agents; D004988:Ethers, Cyclic; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; D019319:Okadaic Acid; D006005:Phosphorylases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; C057862:cyanoginosin LR