Theoretical study of the role of low-barrier hydrogen bonds in enzyme catalysis: a model of proton transfer in serine protease

A model of low-barrier hydrogen bonds (LBHBs) in enzymes has been studied b y ab initio quantum mechanical calculations including the self-consistent r eaction field solvent model. The hydrogen-bond strengths and the deprotonat ion energies for the hydrogen-bonded and non-hydrogen-bonded cis-urocanic a cid were calculated at the HF/6-31 + G(d,p) level at various dielectric con stants. The same calculations were performed for the alpha,beta -dihydrouro canic acid to model the catalytic dyad of serine protease. The deprotonatio n energy of N-epsilon2 in alpha,beta -dihydrourocanic acid is increased by formation of LBHBs and depends very much on the dielectric constant. This s tudy suggests that the formation of LBHBs;increases the basicity of the dya d, and the polarity change near the reaction center in the active site coul d help the proton abstraction from Ser 195 and the donation to the leaving group. Both the LBHBs and the environment can play crucial roles in the enz yme catalysis.