QM/MM and free-energy simulations of deacylation reaction catalysed by sedolisin,a serine-carboxyl peptidase

Quantum mechanical/molecular mechanical free-energy simulations were performed to understand the deacylation reaction catalysed by sedolisin (a serine-carboxyl peptidase) and to elucidate the catalytic mechanism and the role of the active-site residues during the process. The results given here demonstrate that Asp170 may act as a general acid/base catalyst for the deacylation reaction. It is also shown that the electrostatic oxyanion hole interactions involving Asp170 may be less effective in transition state stabilisation for the deacylation step in the sedolisin-catalysed reaction compared to the general acid/base mechanism. The proton transfer processes during the enzyme-catalysed process were examined, and their role in the catalysis was discussed.