Showdomycin, a nucleotide-site-directed inhibitor of (Na+ + K+)-ATPase.
Showdomycin [2-(beta-D-ribofuranosyl)maleimide] is a nucleoside antibiotic containing a maleimide ring and which is structurally related to uridine. Showdomycin inhibited rat brain (Na+ + K+)-ATPase irreversibly by an apparently bimolecular reaction with a rate constant of about 11.01-mol- minus 1-min- minus 1. Micromolar concentrations of ATP protected against this inhibition but uridine triphosphate or uridine were much less effective. In the presence of K+, 100 MUM ATP was unable to protect against inhibition by showdomycin. These observations show that showdomycin inhibits (Na+ + K+)-ATPase by reacting with a specific chemical group or groups at the nucleotide-binding site on this enzyme. Inhibition by showdomycin appears to be more selective for this site than that due to tetrathionate or N-ethylmaleimide. Since tetrathionate is a specific reactant for sulfhydryl groups it appears likely that the reactive groups are sulfhydryl groups. The data thus show that showdomycin is a relatively selective nucleotide-site-directed inhibitor of (Na+ + K+)-ATPase and inhibiton is likely due to the reaction of showdomycin with sulfhydryl group(s) at the nucleotide-binding site on this enzyme.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology; D008623:Mercaptoethanol / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D012787:Showdomycin / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013776:Tetrathionic Acid / Q000494:pharmacology; D014500:Uracil Nucleotides / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D013438:Sulfhydryl Compounds; D014500:Uracil Nucleotides; D008623:Mercaptoethanol; D000255:Adenosine Triphosphate; D013776:Tetrathionic Acid; D012964:Sodium; D012787:Showdomycin; D000251:Adenosine Triphosphatases; D005033:Ethylmaleimide; D011188:Potassium