Enzymatic transition states and inhibitor design from principles of classical and quantum chemistry

A procedure is described which leads to experimentally based models for the transition‐state structures of enzyme‐catalyzed reactions. Substrates for an enzymic reaction are synthesized with isotopically enriched atoms at every position in which bonding changes are anticipated at the enzyme‐enforced transition state. Kinetic isotope effects are measured for each atomic substitution and corrected for diminution of the isotope effects from …