A density functional theory study on the intramolecular proton transfer in the enzyme carbonic anhydrase

作者：Chen H; Li SH^*; Jiang YS

来源：Journal of Physical Chemistry A, 2003, 107(23): 4652-4660.

DOI：10.1021/jp026788k

Density functional calculations are used to explore the mechanism of the intramolecular proton transfer (PT) from Zn-bound H2O to the proton acceptor His64 in the enzyme carbonic anhydrase (CA). By performing free and restricted geometry optimizations on the model system (Im(3))(3)Zn2+...(OH2)(3)...Im (Im is imidazole), we determine the PT potential energy profiles under three conditions: (a) without geometric restrictions, (b) with the proton donor-acceptor distance fixed, and (c) with the relative orientation of the imidazole acceptor fixed. The latter two circumstances are invoked to mimic the effect of the protein framework on the PT energy surface. Our calculations indicate that the PT process involves a concerted mechanism under all three of these conditions. If we take into account the effects of the protein framework, the protein electrostatic environment, and zero-point vibrational energies altogether, we obtain a reasonable estimate of similar to7 kcal/mol for the PT barriers in both hydration and dehydration directions, which agree well with the experimental values. In addition, the influence of the nearby residues or surrounding water molecules on the PT energy surface is modeled by adding two side waters to the water chain of the model system. Calculations suggest that if the hydrogen bond interaction between the side water (or any other residue) and the water in the water bridge is sufficiently strong a two-step proton transfer mechanism is favored; otherwise, the intramolecular proton transfer may still occur in a concerted way.

• 出版日期2003-6-12
• 单位南京大学