ABSTRACT
Enzymes display a variety of remarkable catalytic functions essen-
tial for cell viability and reproduction. Understanding the origin
of enzymatic rate enhancement has been a goal of biochemistry
for more than half a century. Initial attempts to understand
enzyme mechanisms were based on steady-state kinetics studies
that provided a measure of the catalytic efficiency characterized
by turnover number and the strength of substrate binding. Along
with direct studies of enzymes, the combination of physical organic
chemistry with protein structure fostered the hypothesis that the
catalytic efficiency of enzymes was attributable to the restriction of
substrate rotations and the orientation of catalytic groups within
the active site. To facilitate an optimal low-energy transition state,
a more complete molecular description of catalysis is developed
through progress in rapid transient kinetics methods that extended
the time range available for observation, leading to the discovery of
intermediates that virtually occur in every enzyme catalytic cycle.
