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

Journal Article · Sat Feb 01 04:00:00 EST 1997 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/ja9630250· OSTI ID:1508291

Wu, Qinyuan; Gao, Jinming; Joseph-McCarthy, Diane; Sigal, George B.; Bruce, James E.; Whitesides, George M.; Smith, Richard D.

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1508291
• Report Number(s): PNNL-SA-28047
• Journal Information: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 5 Vol. 119; ISSN 0002-7863
• Publisher: American Chemical Society (ACS)
• Country of Publication: United States
• Language: English