Study of Non‐Covalent Enzyme‐Inhibitor Complexes of Aldose Reductase by Electrospray Mass Spectrometry
- 1 January 1997
- journal article
- Published by Wiley in European Journal of Biochemistry
- Vol. 243 (1-2) , 274-282
- https://doi.org/10.1111/j.1432-1033.1997.0274a.x
Abstract
Specific non‐covalent interactions between aldose reductase (AR), its NADP+ cofactor and five inhibitors have been characterized by electrospray mass spectrometry (ES‐MS). These results indicated that the protein could be desorbed and maintained in the gas phase in a form very close to its native conformation. Collisionally induced dissociation (CID)‐MS and CID‐MS‐MS showed that the adenosine diphospbate part of the cofactor interacts strongly with AR. The relative stability of the ternary AR NADP+ inhibitor complexes was established and successfully correlated with the IC50, values. All inhibitors were shown to only bind to AR holoenzyme. These results are important for the field of drug development insofar as ES‐MS might provide a rapid and very sensitive method for the screening of potential drugs or for the identification of compounds displaying high binding affinity to a target biomolecule.Keywords
This publication has 29 references indexed in Scilit:
- Investigation of non‐covalent ligand binding to the intact streptavidin tetramer by electrospray ionization mass spectrometryJournal of Mass Spectrometry, 1995
- Observation of large subunit protein complexes by electrospray ionization mass spectrometryJournal of Mass Spectrometry, 1995
- Analysis of the Energetics of Gas-Phase Immunophilin-Ligand Complexes by Ion Spray Mass SpectrometryJournal of the American Chemical Society, 1994
- Observation of the Noncovalent Quaternary Associations of Proteins by Electrospray Ionization Mass SpectrometryJournal of the American Chemical Society, 1994
- Observation of large multimers in the electrospray ionization mass spectrometry of peptidesRapid Communications in Mass Spectrometry, 1994
- Mass spectrometric studies on noncovalent dimers of leucine zipper peptidesJournal of the American Chemical Society, 1993
- Observation of the multimeric forms of concanavalin A by electrospray ionization mass spectrometryJournal of the American Chemical Society, 1993
- Purification and electrospray mass spectrometry of aldose reductase from pig lensBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1992
- Preservation of non‐covalent associations in electrospray ionization mass spectrometry: Multiply charged polypeptide and protein dimersJournal of Mass Spectrometry, 1992
- Detection of noncovalent receptor-ligand complexes by mass spectrometryJournal of the American Chemical Society, 1991