Structural Biochemistry/Enzyme/Transition-State Binding Principle

The enzyme associated in the transition-state stabilization binds to the transition state better than when it binds to the ground-state reactants. The enzyme is seen as a flexible molecule where its shape is complementary to the substrates or reactants when in its activated transition-state. As the enzyme binds to the transition state the reaction is accelerated proportionate to the transition state concentration.

The transition state compared to the ground state was first introduced by Kurz in 1963. In 1966 Jencks then introduced the existence of transition-state-analog inhibitors. Transition-state theory started to have more emphasis on enzymology in the 1970s when scientists started to notice the broad power of transition-state analogs.

The first three-dimensional structure of the transition-state geometry studied was the lysozyme of a hen egg-white. They observed and studied the x-ray crystallography and visualized the complementarity of a catalytic site to the transition-state geometry. Scientists studied the binding of many oligosaccharide inhibitors and showed how substrates bind to the lysozyme. Furthermore, they deduced that the conformation of a sugar residue strongly effects the binding to the enzyme. When the sugar residue was in its half-hair conformation, then binding occurs.

Transition-state theory relies on assumptions and approximations. The two assumptions include a dynamical bottleneck assumption and an equilibrium assumption. Dynamic bottleneck states the decomposition of a transition-state complex controls the reate rate. The equilirium assumption states that the transition-state molecule is in equilibrium with the reactants.

Through thermodynamic cycling, transition-state theory can be applied to enzyme catalysis.