Showdomycin [2-(β-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-1·min-1. Micromolar concentrations of ATP protected against this inhibition but uridine triphosphate or uridine were much less effective. In the presence of K+, 100 μM 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 inhibition is likely due to the reaction of showdomycin with sulfhydryl group(s) at the nucleotide-binding site on this enzyme.
|Number of pages||11|
|Journal||BBA - Biomembranes|
|State||Published - Apr 21 1975|
Bibliographical noteFunding Information:
This work was supported by grants from the Michigan Heart Association, Grant H. L. 16055-01 from the National Institutes of Health, and General Research Support Grant NIH RR 05623-04 to the College of Veterinary Medicine, Michigan State University, from the National Institutus of Health. The authors would like to thank Dr Theodore M. Brody for helpful suggestions and for reviewing the manuscript, and Mrs Annie Han and Mrs Marilyn Turnbow for excellent technical assistance.
ASJC Scopus subject areas
- Cell Biology