A novel electrostatic approach to enzyme mechanisms: carbonic anhydrase as an example.

A novel electrostatic approach to the manner in which enzymes catalyze reactions is developed. In this development, the author's interpretations of, and additions to, the late K. Fajans' theory of electronic structure (referred to as the Quanticule theory of chemical binding) are presented. This theory is based upon electron densities, in analogy to density functional theory. It is used to derive formulations of molecular structure, (Fajans' formulations) which show the charges of the atomic components. These charges are shown to be reduced by polarization to what are commonly referred to as partial charges. These formulations relate to the exchange of charged atomic components during reactions. The relevance of the formulations to the catalytic activity of enzymes is illustrated with carbonic anhydrase. When viewed in terms of Fajans' formulations, the active site is seen to consist of an array of charged atoms. The positive and negative charges tend to alternate. When closely positioned, these charges provide a basis for drawing atomic components of the molecules, which are exchanged in a given reaction, into the new positions. The charges are shown to be related to the binding of substrates to the enzyme and the positioning of them so that they can interact, to the reaction itself, to an essential proton transfer, and to the dissociation of the product from the enzyme. This more extensive scope of electrostatic interactions provides a more simple view of the manner in which the catalysis is accomplished. Such catalysis is consistent with a number of other proposals about enzyme mechanisms, and appears to be applicable to a large majority of enzyme-catalyzed reactions.