The enigmatic conservation of enzyme dynamics in evolution

SummaryExamination of the chemical step catalysed by dihydrofolate reductase (DHFR) suggested preservation of an “ideal” transition state as the enzyme evolves from bacteria to human. This observation is enigmatic: since evolutionary pressure is most effective on enzymes' second order rate constant (kcat/KM) and since the chemistry is not rate limiting on that kinetic parameter, why is the nature of the chemical step preserved? Studies addressing this question were presented in the 2015 Beilstein ESCEC Symposium and are summarized below.