Protein dynamics and catalysis: the problems of transition state theory and the subtlety of dynamic control.
This manuscript describes ongoing research on the nature of chemical reactions in enzymes. We will investigate how protein dynamics can couple to chemical reaction in an enzyme. We first investigate in some detail why transition state theory cannot fully describe the dynamics of chemical reactions catalysed by enzymes. We describe quantum theories of chemical reaction in condensed phase including studies of how the symmetry of coupled vibrational modes differentially affects reaction dynamics. We make reference to previous work in our group on a variety of condensed phase chemical reactions (liquid and crystalline) and a variety of enzymatically catalysed reactions including the reactions of lactate dehydrogenase and purine nucleoside phosphorylase. All the protein motions we have studied have been quite rapid. We will propose methods to find motions over a broad range of time-scales in enzymes that couple to chemical catalysis. We report recent findings which show that conformational fluctuations in lactate dehydrogenase can strongly affect its ability to catalyse reactions through protein motion, and that only a tiny minority of conformations appear to be catalytically competent.
Pineda
J R E T
JR
Department of Biophysics, Seaver Foundation Center for Bioinformatics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Schwartz
S D
SD
D002384:Catalysis; D004798:Enzymes / Q000737:chemistry*; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D008956:Models, Chemical; D011487:Protein Conformation; D011789:Quantum Theory
D004798:Enzymes; D007770:L-Lactate Dehydrogenase