In this report, we compare the kinetic stabilities of nonco-valent complexes between bovine carbonic anhydrase II (BCAII,EC 4.2.1.1) andpara-substituted benzenesulfonamide inhibitors4in the gas phase and in solution. These BCAII-inhibitorsystems are attractive model systems due to the stability ofcarbonic anhydrase (CA) and its well characterized structureand ligand complexes, providing a basis for inferences regardingthe protein structure in the gas phase and its ligand interactions.CA is a roughly spherical Zn(II) metalloenzyme having a conicalbinding pocket which catalyzes the hydration of CO2to bi-carbonate. A large body of data correlate structures of sul-fonamide ligands with their binding constants to CA.5A setof eight inhibitors was selected for this study, covering a widerange of binding affinities and varying in the length of their ails and aromatic content. The results demonstrate that relativestabilities of BCAII-inhibitor complexes differ substantiallybetween the gas and liquid phases and also show the dominantrole of polar surface interactions in the gas phase.
Revised: April 23, 2019 |
Published: February 5, 1997
Citation
Wu Q., J. Gao, D. Joseph-Mccarthy, G.B. Sigal, J.E. Bruce, G.M. Whitesides, and R.D. Smith. 1997.Carbonic Anhydrase-Inhibitor Binding: From Solution to the Gas Phase.Journal of the American Chemical Society 119, no. 5:1157-1158.PNNL-SA-28047.doi:10.1021/ja9630250