| Citation | Distinguished for work on mechanisms of enzyme catalysis, especially by stopped and quenched flow methods. He showed that a slow relaxation of chymotrypsin was not a chemical step on the reaction pathway, but a pH-dependent isomerization between active and inactive forms, and investigated the energetics and equilibria of the transition. He elucidated the leaving-group specificity, leading to a detailed structural interpretation which showed the energetics of "strain" at the binding site. Another experiment dispelled final doubts about the role of a tetrahedral intermediate. More recently Fersht has studied a more complex group of enzymes, the aminoacyl tRNA synthetases. He demonstrated that their precise specificity depends on consecutive independent recognition steps, and under appropriate conditions he trapped a transiently mischarged aminoacyl tRNA. Fersht has shown how binding energy can be used to enhance either specificity or rate in an enzymatic reaction, leading to a demonstration of thermodynamic limitations on mechanisms of the "induced fit" type. |