skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

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.

Authors:
; ;  [1]; ; ; ;  [2]
  1. Pacific Northwest National Lab., Richland, WA (United States)
  2. Harvard Univ., Cambridge, MA (United States)
Publication Date:
OSTI Identifier:
460043
DOE Contract Number:  
AC06-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of the American Chemical Society
Additional Journal Information:
Journal Volume: 119; Journal Issue: 5; Other Information: PBD: 5 Feb 1997
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; 40 CHEMISTRY; CARBONIC ANHYDRASE; BIOCHEMICAL REACTION KINETICS; PHASE TRANSFORMATIONS; SOLUTIONS; GASES; PROTEINS; LIGANDS; CATTLE; INHIBITION; ENZYME INHIBITORS; AMINO ACIDS; COMPLEXES; NUMERICAL DATA

Citation Formats

Wu, Q, Bruce, J E, Smith, R D, Gao, J, Joseph-McCarthy, D, Sigal, G B, and Whitesides, G M. Carbonic anhydrase-inhibitor binding: From solution to the gas phase. United States: N. p., 1997. Web. doi:10.1021/ja9630250.
Wu, Q, Bruce, J E, Smith, R D, Gao, J, Joseph-McCarthy, D, Sigal, G B, & Whitesides, G M. Carbonic anhydrase-inhibitor binding: From solution to the gas phase. United States. https://doi.org/10.1021/ja9630250
Wu, Q, Bruce, J E, Smith, R D, Gao, J, Joseph-McCarthy, D, Sigal, G B, and Whitesides, G M. 1997. "Carbonic anhydrase-inhibitor binding: From solution to the gas phase". United States. https://doi.org/10.1021/ja9630250.
@article{osti_460043,
title = {Carbonic anhydrase-inhibitor binding: From solution to the gas phase},
author = {Wu, Q and Bruce, J E and Smith, R D and Gao, J and Joseph-McCarthy, D and Sigal, G B and Whitesides, G M},
abstractNote = {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.},
doi = {10.1021/ja9630250},
url = {https://www.osti.gov/biblio/460043}, journal = {Journal of the American Chemical Society},
number = 5,
volume = 119,
place = {United States},
year = {1997},
month = {2}
}