Induced fit or conformational selection, the case of Na,K-ATPase phosphorylation

FARAJ SE; ROSSI RC; MONTES MR

Buenos Aires

Congreso; 2nd Protein Biophysics at the End of the World; 2017

Ernesto A. Roman, Diego U. Ferreiro, César Ramirez-Sarmiento, Christian Wilson

The binding of ligands by macromolecules is crucial to a multitude of physiological processes. In virtually all cases, the binding of ligands and conformational changes go hand in hand. The 2 limiting cases are the "induced fit" mechanism (binding first) or "conformational selection" (conformational change first). Recently, Tummino and Copeland (2008) pointed out that induced fit is by far the most common mechanism of recognition documented experimentally, with conformational selection being confined to a handful of cases. This conclusion was based on the results of kinetics analyzed under the rapid equilibrium approximation where the rate of approach to equilibrium (kobs) decreases with ligand concentration. In this work we analyzed the kinetic of binding of Pi and Pi-like ligands (BeF3) to the Na,K-ATPase and evaluated the possible models to explain the results. We observed that although the kobs decreases with [Pi] and increases with [BeF3], both processes may be explained by a "conformational selection model" if the rapid equilibrium approximation is not invoked.