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 F(1) to rotation of the gamma subunit during ATP synthesis and hydrolysis catalyzed by the F(o)F(1)-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 MF(1) and wild-type and mutant alpha(3)beta(3)gamma subcomplexes of TF(1) are also reviewed. From these considerations, it is concluded that Mg-ADP-fluoroaluminate complexes formed at catalytic sites of isolated F(1)-ATPases or F(1) in membrane-bound F(o)F(1) are ground-state analogs.