Carbonic anhydrase-inhibitor binding: From solution to the gas phase

Journal Article · Wed Feb 05 04:00:00 EST 1997 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/ja9630250· OSTI ID:460043

Wu, Q; Bruce, J E; Smith, R D ^[1]; Gao, J; Joseph-McCarthy, D; Sigal, G B; Whitesides, G M ^[2]

---

1. Pacific Northwest National Lab., Richland, WA (United States)
2. Harvard Univ., Cambridge, MA (United States)

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.

• DOE Contract Number: AC06-76RL01830
• OSTI ID: 460043
• Journal Information: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 5 Vol. 119; ISSN JACSAT; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

40 CHEMISTRY
55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
BIOCHEMICAL REACTION KINETICS
CARBONIC ANHYDRASE
CATTLE
COMPLEXES
ENZYME INHIBITORS
GASES
INHIBITION
LIGANDS
NUMERICAL DATA
PHASE TRANSFORMATIONS
PROTEINS
SOLUTIONS