Covalent Intermediates and Enzyme Proficiency

摘要

How enzymes catalyze reactions has been of great interest for over a hundred years. Both ground state and transition state contributions to the rate of enzyme-catalyzed reactions have been considered. In 1894, Emil Fischer proposed that the substrate fits into the enzyme like a key fits into a lock. In the language of the present age, the Fischer proposal would be: substrate conformers resembling the transition state fit the enzyme active site like a key fits a lock but with a little wiggle. Such conformers have been called near attack conformers (NACs) and are readily observed by molecular dynamics. The free energy (ΔG) for conversion of the Michaelis complex (E·S) to the enzyme transition state complex (E·TS) is the sum of the standard free energy for NAC formation plus the free energy of activation for E·NAC → E·TS (eq 1).