Model studies on the active site of carbonic anhydrase: Ligand properties and CO2 binding

Abstract

AbstractIn view of building a workable molecular model of tetraliganded zinc at the active site of carbonic anhydrase, an ab initio SCF study using pseudopotentials is performed on Zn2+(OH2)n from n = 2 to 6, Zn2+(NH3)n−1 (OH2) for n = 2 and 4, Zn2+(NH3)2 (imidazole) (OH2), and their ionized species involving OH− or imidazolate, considering in particular the evolution of the properties of the ligands and of the bound cation upon increasing n and upon replacement of one ligand by another. (Comparison of NH3 and imidazole binding was made in a full SCF calculation.) The results obtained in the tetraliganded complex confirm that zinc binding facilitates water deprotonation more than imidazole deprotonation, so as to reverse the order of their intrinsic ease of ionization. A study of the approach of CO2 toward the active site is made in an electrostatic approximation using as models the most representative of the computed four‐ligand complexes.