Research Interest:

Basic Features of the ATP Synthase Catalysis The membrane-bound ATP synthase of animals, plants, and microorganisms is a highly conserved enzyme with unusual subunit stoichiometry and properties. In the binding change mechanism for the synthase developed by our laboratory, translocation of protons is regarded as driving conformational changes that promote release of a tightly bound ATP at one catalytic site and the tight binding of ADP and P_i at another catalytic site. An interesting speculation is that catalysis is accompanied by a rotational movement of catalytic subunits relative to a noncatalytic core.

Probes of Catalysis and Control We use a combination of chemical derivatization, nucleotide binding and other catalytic site occupancy measurements, conformational and structural probes, subunit isolation and interchange evaluations, subunit cross-linking ¹⁸ O-phosphate exchange measurements, site-specific mutagenesis, and rapid mixing and rate of catalysis approaches. One example is the use of 2-azido ATP and ADP. These are good substrates that when photoactivated covalently modify nucleotide binding sites. Another is the phosphate oxygen exchange methodology that reveals reactions occurring while substrates are still bound and whether the catalysis occurs by one of more pathways.