Mechanical Control of ATP Synthase Function: Activation Energy Difference between Tight and Loose Binding Sites

Despite exhaustive chemical and crystal structure studies, the mechanistic details of how F0F1-ATP synthase call convert mechanical energy to chemical, producing ATP, are still not fully understood. On the basis of quantum mechanical calculations using a recent high-resolution X-ray structure, we conclude that formation of the P-O bond may be achieved through it transition state (TS) with a planar PO3- ion. Surprisingly, there is it more than 40 kJ/mol difference between barrier heights of the loose and tight binding sites of the enzyme. This indicates that even it relatively small change in active site conformation, induced by the gamma-subunit rotation, may effectively block the back reaction in beta(TP) and, thus, promote ATP.