Inhibition of Na,K-ATPase by a new ATP analog, adenosine-5-N'-(2,4-dinitro-5-fluorophenyl)phosphohydrazide.
A new ATP analog, adenosine-5-N'-(2,4-dinitro-5-fluorophenyl) phosphohydrazide (DNPH-AMP), has been synthesized, which is an irreversible inhibitor of Na,K-ATPase. Interaction of the analog with the enzyme in the presence of K+ is described by the scheme: [formula: see text] and corresponding kinetic constants k3 and Ki are found equal to 2.5 min-1 and 1.6 mM. In the presence of Na+ the time course of enzyme inactivation by DNPH-AMP is a biphasic curve in the semilogarithmic plot. The k3 and Ki values calculated for this case according to Fritzsch [Fritzsch (1985) J. Theor. Biol. 117, 397] are equal to 2.45 min-1 and 2.5 mM, respectively. ATP transforms the K(+)-type of Na,K-ATPase inactivation into the one that takes place in the presence of Na+.
Lopina
O
O
Institute of Biochemistry, USSR Academy of Sciences, Moscow.
Skackova
D
D
Baranova
L
L
Khropov
Y
Y
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D004372:Ducks; D066298:In Vitro Techniques; D007700:Kinetics; D011487:Protein Conformation / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
C068985:adenosine-5-N'-(2,4-dinitro-5-fluorophenyl)phosphohydrazine; D012965:Sodium Chloride; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase