INVESTIGATION OF FLUORIDE INTERACTION WITH THE ACTIVE SITE OF THE ENZYME MYELOPEROXIDASE USING MAGNETIC RESONANCE

Atrium

Objective. This study was conducted in order to determine the nature of the interaction of fluoride with the active site of myeloperoxidase. A secondary issue is to address whether fluoride could act as a means of modulating the activity of this enzyme in vivo. Background. Although myeloperoxidase is beneficially involved in antimicrobial and cytotoxic activities, it is also thought to be involved in causing and destabilizing cardiovascular plaques. In recent years, techniques have been developed to image myeloperoxidase in situ in plaques, and measurement of plasma concentrations of the enzyme has been suggested as a means of detecting cardiovascular disease. Since fluoride is known to be an inhibitor of myeloperoxidase, it is of interest to study the interaction of fluoride with the active site. Methods. In this study proton and 19F nuclear magnetic resonance as well as electron spin resonance approaches were utilized. Spin-lattice relaxation times of solvent water protons and fluoride ions were measured in the presence and absence of myeloperoxidase. Electron spin resonance spectra of myeloperoxidase were obtained in the presence and absence of fluoride. Results. The presence of fluoride has a minor effect on diminishing the proton relaxation rate of solvent water protons in myeloperoxidase solutions. The presence of fluoride has a dramatic effect upon electron spin resonance spectra of the enzyme causing the rhombic splitting to be reduced. Conclusion. These data suggest that fluoride does not block water exchange with the heme site, but diminishes the asymmetry of the charge distribution in the plane of the heme. Grants. NSU Faculty Research Grant