Carbonic Anhydrase-Inhibitor Binding: From Solution to the Gas Phase

In this report, we compare the kinetic stabilities of noncovalent complexes between bovine carbonic anhydrase II(BCAII, EC 4.2.1.1) and para-substituted benzenesulfonamide inhibitors in the gas phase and in solution. These BCAII-inhibitor systems are attractive model systems due to the stability of carbonic anhydrase (CA) and its well characterized structure and ligand complexes, providing a basis for inferences regarding the protein structure in the gas phase and its ligand interactions. CA is a roughly spherical Zn(II) metalloenzyme having a conical binding pocket which catalyzes the hydration of CO{sub 2} to bicarbonate. A large body of data correlate structures of sulfonamide ligands with their binding constants to CA. A set of eight inhibitors was selected for this study, covering a wide range of binding affinities and varying in the length of their tails and aromatic content. The results demonstrate that relative stabilities of BCAII-inhibitor complexes differ substantially between the gas and liquid phases and also show the dominant role of polar surface interactions in the gas phase. 12 refs., 1 fig., 1 tab.