Direct identification of the fluoroaluminate and fluoroberyllate species responsible for inhibition of the mitochondrial F1‐ATPase

[摘要]

In the presence of ADP, fluoroaluminate and fluoroberyllate inhibit irreversibly the soluble mitochondrial F₁-ATPase. We report here direct evidence that this inhibition is related to the tight binding of [³H]ADP, beryllium and fluoride to the enzyme. In the case of beryllium-induced inhibition, the stoichiometry of bound species is 1 mol [³H]ADP, 1 mol beryllium and 2 or 3 mol fluoride depending on the initial fluoride concentration used, which indicates that both the combinations ADP₁,Be₁,F₃ and ADP₁,Be₁,F₃ are competent for inhibition. In the case of aluminium-induced inhibition, the binding stoichiometry of 4 mol fluoride per mol [³H]ADP favours the following combination of bound species ADP₁,Al₁,F₄. These results favour a model where fluorometals mimic phosphate and form an abortive complex with ADP in the catalytic site(s) of F₁.

[学科分类] 生物化学/生物物理

[关键词] Fluoride;Beryllium;Aluminum;ATPase;F1-;Nucleotide analogue;NDP nucleoside diphosphate;NTP nucleoside triph.;pF;colog of the free fluoride concentration;CDTA trans-1;2 diaminocyclohexane-N;N;N′;N′-tetraacetic acid