The catalytic transition state in ATP synthase

The catalytic transition state of ATP synthase has been characterized and modeled by combined use of (1) Mg-ADP-fluoroaluminate, Mg-ADP-fluoroscandium, and corresponding Mg-IDP-fluorometals as transition-state analogs: (2) fluorescence signals of β-Trp331 and β-Trp148 as optical probes to assess formation of the transition state: (3) mutations of critical catalytic residues to determine side-chain ligands required to stabilize the transition state. Rate acceleration by positive catalytic site cooperativity is explained as due to mobility of α-Arg376, acting as an "arginine finger" residue, which interacts with nucleotide specifically at the transition state step of catalysis, not with Mg-ATP- or Mg-ADP-bound ground states. We speculate that formation and collapse of the transition state may engender catalytic site α/β subunit-interface conformational movement, which is linked to γ-subunit rotation.