Short-strong hydrogen bonds and a low barrier transition state for the proton transfer reaction in RNase A catalysis: a quantum chemical study

There is growing evidence that some enzymes catalyze reactions through the formation of short-strong hydrogen bonds as first suggested by Gerlt and Ga ssman. Support comes from several experimental and quantum chemical studies that include correlation energies on model systems. In the present study, the process of proton transfer between hydroxyl and imidazole groups. a mod el of the crucial step in the hydrolysis of RNA by the enzymes of the RNase A family. is investigated at the quantum mechanical level of density funct ional theory and perturbation theory at the MP2 level, The model focuses on the nature of the formation of a complex between the important residues of the protein and the hydroxyl group of the substrate. We have also investig ated different configurations of the ground state that are important in the proton transfer reaction. The nature of bonding between the catalytic unit of the enzyme and the substrate in the model is investigated by Bader's at oms in molecule theory. The contributions of solvation and vibrational ener gies corresponding to the reactant. the transition state: and the product c onfigurations are also evaluated. Furthermore. the effect of protein enviro nment is investigated by considering the catalytic unit surrounded by compl ete proteins-RNase A and Angiogenin. The results, in general, indicate the formation of a short-strong hydrogen bond and the formation of a low barrie r transition state fur the proton transfer model of the enzyme. (C) 2001 El sevier Science B.V. All rights reserved.