Evolutionary Aspects of Enzyme Dynamics [Molecular Biophysics]

September 10th, 2014 by Klinman, J. P., Kohen, A.

The role of evolutionary pressure on the chemical step catalyzed by enzymes is somewhat enigmatic, in part because chemistry is not rate-limiting for many optimized systems. Herein, we present studies that examine various aspects of the evolutionary relationship between protein dynamics and the chemical step in two paradigmatic enzyme families, dihydrofolate reductases and alcohol dehydrogenases. Molecular details of both convergent and divergent evolution are beginning to emerge. The findings suggest that protein dynamics across an entire enzyme can play a role in adaptation to differing physiological conditions. The growing tool kit of kinetics, kinetic isotope effects, molecular biology, biophysics and bioinformatics provides a means to link evolutionary changes in structure-dynamics-function to each proteins vibrational and conformational states.