Tightly bound adenosine diphosphate, which inhibits the activity of mitochondrial F1‐ATPase, is located at the catalytic site of the enzyme

• Published in: FEBS letters 1985-03, Vol.182 (2), p.419-424
• Main Authors: Drobinskaya, I.Ye, Kozlov, I.A., Murataliev, M.B., Vulfson, E.N.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; ADP inhibition; Analytical, structural and metabolic biochemistry; Animals; Binding Sites; Biological and medical sciences; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Guanosine Diphosphate - metabolism; Guanosine Triphosphate - metabolism; Guanosine Triphosphate - pharmacology; Hydrolases; Kinetics; Magnesium - pharmacology; Mitochondria - enzymology; Mitochondrial F1-ATPase; Nucleotide binding; Phosphate binding; Phosphates - metabolism; Proton-Translocating ATPases - antagonists & inhibitors; Proton-Translocating ATPases - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(85)80346-X

The binding of one ADP molecule at the catalytic site of the nucleotide depleted F1‐ATPase results in a decrease in the initial rate of ATP hydrolysis. The addition of an equimolar amount of ATP to the nucleotide depleted F1‐ATPase leads to the same effect, but, in this case, inhibition is time dependent. The half‐time of this process is about 30 s, and the inhibition is correlated with Pi dissociation from the F1‐ATPase catalytic site (uni‐site catalysis). The F1‐ATPase‐ADP complex formed under uni‐site catalysis conditions can be reactivated in two ways: (i) slow ATP‐dependent ADP release from the catalytic site (τ½ 20 s) or (ii) binding of Pi in addition to MgADP and the formation of the triple F1‐ATPase‐MgADP‐Pi complex. GTP and GDP are also capable of binding to the catalytic site, however, without changes in the kinetic properties of the F1‐ATPase. It is proposed that ATP‐dependent dissociation of the F1‐ATPase‐GDP complex occurs more rapidly, than that of the F1‐ATPase‐ADP complex.