Inhibitory Mg-ADP-fluoroaluminate complexes bound to catalytic sites of F(1)-ATPases: are they ground-state or transition-state analogs?

Schemes are proposed for coupling sequential opening and closing the three catalytic sites of F1 to rotation of the γ subunit during ATP synthesis and hydrolysis catalyzed by the FoF1-ATP synthase. A prominent feature of the proposed mechanisms is that the transition state during ATP synthesis is formed when a catalytic site is in the process of closing and that the transition state during ATP hydrolysis is formed when a catalytic site is in the process of opening. The unusual kinetics of formation of Mg-ADP—fluoroaluminate complexes in one or two catalytic sites of nucleotide-depleted MF1 and wild-type and mutant α3β3γ subcomplexes of TF1 are also reviewed. From these considerations, it is concluded that Mg-ADP—fluoroaluminate complexes formed at catalytic sites of isolated F1-ATPases or F1 in membrane-bound FoF1 are ground-state analogs.