Role of conformational dynamics in kinetics of an enzymatic cycle in a nonequilibrium steady state.
Enzyme is a dynamic entity with diverse time scales, ranging from picoseconds to seconds or even longer. Here we develop a rate theory for enzyme catalysis that includes conformational dynamics as cycling on a two-dimensional (2D) reaction free energy surface involving an intrinsic reaction coordinate (X) and an enzyme conformational coordinate (Q). The validity of Michaelis-Menten (MM) equation, i.e., substrate concentration dependence of enzymatic velocity, is examined under a nonequilibrium steady state. Under certain conditions, the classic MM equation holds but with generalized microscopic interpretations of kinetic parameters. However, under other conditions, our rate theory predicts either positive (sigmoidal-like) or negative (biphasic-like) kinetic cooperativity due to the modified effective 2D reaction pathway on X-Q surface, which can explain non-MM dependence previously observed on many monomeric enzymes that involve slow or hysteretic conformational transitions. Furthermore, we find that a slow conformational relaxation during product release could retain the enzyme in a favorable configuration, such that enzymatic turnover is dynamically accelerated at high substrate concentrations. The effect of such conformation retainment in a nonequilibrium steady state is evaluated.
Min
Wei
W
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. weimin@fas.harvard.edu
Xie
X Sunney
XS
Bagchi
Biman
B
D055162:Biocatalysis; D004798:Enzymes / Q000378:metabolism*; D007700:Kinetics; D011487:Protein Conformation; D013816:Thermodynamics
D004798:Enzymes