Catalytic role of enzymes: Short strong H-bond-induced partial proton shuttles and charge redistributions

A two-step reaction mechanism (catalyzed alternatively by acid and base) wi th partial proton shuttles and charge redistributions promoted by short str ong H bonds (SSHBs) (playing a dual role as an amphi-acid/base catalyst) is proposed to explain the enormous rate enhancement observed in enzymatic re actions involving carbanion intermediates. The SSHBs in the two-step reacti ons are found to be responsible for enhancing enzyme-substrate interactions in favor of the transition state structure over that of reactant, The deta iled quantum theoretical studies of ketosteroid isomerase provide evidence of assisting roles of SSHB in enzymatic activity. The understanding of the two-step reaction mechanism would be a useful aid in designing novel functi onal enzymes and abzymes.