Ia. Gorshkova et al., Halenaquinol, a natural cardioactive pentacyclic hydroquinone, interacts with sulfhydryls on rat brain Na+,K+-ATPase, COMP BIOC C, 128(4), 2001, pp. 531-540
Citations number
39
Categorie Soggetti
Pharmacology & Toxicology
Journal title
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
Halenaquinol inhibited the partial reactions of ATP hydrolysis by rat brain
cortex Na+,K+-ATPase, such as [H-3]ATP binding to the enzyme. Na+-dependen
t front-door phosphorylation from [gamma-P-33]ATP, and also Na+- and K+-dep
endent E-1 <----> E-2 conformational transitions of the enzyme. Halenaquino
l abolished the positive cooperativity between the Na+- and K+-binding site
s on the enzyme. ATP and sulfhydryl-containing reagents (cysteine and dithi
othreitol) protected the Na+,K+-ATPase against inhibition, Halenaquinol can
react with additional vital groups in the enzyme after blockage of certain
sulfhydryl groups with 5,5'-dithio-bis-nitrobenzoic acid. Halenaquinol inh
ibited [H-3]ouabain binding to Na+,K+-ATPase under phosphorylating and non-
phosphorylating conditions. Binding of fluorescein 5'-isothiocyanate to Na,K+-ATPase and intensity of fluorescence of enzyme tryptophanyl residues we
re decreased by halenaquinol. We suggest that interaction of halenaquinol w
ith the essential sulfhydryls in/or near the ATP-binding site of Na+,K+-ATP
ase resulted in a change of protein conformation and subsequent alteration
of overall and partial enzymatic reactions, (C) 2001 Elsevier Science Inc.
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