Toward an adequate scheme for the ATP synthase catalysis

The suggestions from the author's group over the past 25 years for how step s in catalysis by ATP synthase occur are reviewed. Whether rapid ATP hydrol ysis requires the binding of ATP to a second site (bi-site activation) or t o a second and third site (tri-site activation) is considered. Present evid ence is regarded as strongly favoring bi-site activation. Presence of nucle otides at three sites during rapid ATP hydrolysis can be largely accounted for by the retention of ADP formed and/or by the rebinding of ADP formed. M enz, Leslie and Walker ((2001) FEBS Lett., 494, 11-14) recently attained ai l X-ray structure of a partially closed enzyme form that binds ADP better t han ATP. This accomplishment and other considerations form the base for a r evised reaction sequence. Three types of catalytic sites are Suggested, sim ilar to those proposed before the X-ray data became available. During net A TP synthesis a partially closed site readily binds ADP and Pi but not ATP. At a closed site, tightly bound ADP and Pi are reversibly converted to tigh tly bound ATP. ATP is released from a partially closed site that can readil y bind ATP or ADP, ATP hydrolysis when protonmotive force is low or lacking occurs simply by reversal of all steps with the opposite rotation of the g amma subunit. Each type of site can exist in various conformations or forms as they are interconverted during a 120 degrees rotation. The conformation al changes with the ATP synthase, including the vital change when bound ADP and P-i are converted to bound ATP, are correlated with those that occur i n enzyme catalysis in general, as illustrated by recent Studies of Rose wit h fumarase. The beta (E) structure of Walker's group is regarded as all unl ikely, or only quite transient, intermediate. Other X-ray structures are re garded as closely resembling but not identical with certain forms participa ting in catalysis. Correlation of the suggested reaction scheme with other present information is considered.