Catalytic site forms and controls in ATP synthase catalysis

A suggested minimal scheme for substrate binding by and interconversion of three forms of the catalytic sites of the ATP synthase is presented. Each b inding change, that drives simultaneous interchange of the three catalytic site forms, requires a 120 degrees rotation of the gamma with respect to th e beta subunits. The binding of substrate(s) at two catalytic sites is rega rded as sufficing for near maximal catalytic rates to be attained. Although three sites do not need to be filled for rapid catalysis, during rapid bis ite catalysis some enzyme may be transiently present with three sites fille d. Forms with preferential binding for ADP and Pi or for ATP are considered to arise from the transition state and participate in other steps of the c atalysis. Intermediate forms and steps that may be involved are evaluated. Experimental evidence for energy-dependent steps and for control of couplin g to proton translocation and transition state forms are reviewed. Impact o f relevant past data on present understanding of catalytic events is consid ered. In synthesis a key step is suggested in which proton translocation be gins to deform an open site so as to increase the affinity for ADP and P-i, that then bind and pass through the transition state, and yield tightly bo und ATP in one binding change. ADP binding appears to be a key parameter co ntrolling rotation during synthesis. In hydrolysis ATP binding to a loose s ite likely precedes any proton translocation, with proton movement occurrin g as the tight site form develops. Aspects needing further study are noted. Characteristics of the related MgADP inhibition of the F-1 ATPases that ha ve undermined many observations are summarized. and relations of three-site filling to catalysis are assessed. (C) 2000 Elsevier Science B.V. All righ ts reserved.