STRUCTURE AND FUNCTION OF MYELOPEROXIDASE

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The objective of this application is to delineate the molecular mechanism of the enzyme action. of myeloperoxidase, which is one of the major components of the antimicrobial system of polymorphonuclear neutrophils. One of the important properties of myeloperoxidase is its ability to catalyze the formation of hypochlorous acid from hydrogen peroxide and chloride ion to kill the ingested organism. The primary goals of this research proposal are: (i) determination of the structure of the myeloperoxidase heme group by use of the heme-peptide prepared by proteolytic digestion of the enzyme protein, (ii) characterization of the effect of the specific modification of the heme group on the structure and function of myeloperoxidase by use of the novel photochemically modified myeloperoxidase preparation, and (iii) detailed elucidation of the active site structure of myeloperoxidase with reference to other mammalian peroxidase enzymes to understand the distinct function of this enzyme. We plan to use optical absorption, resonance Raman, electron paramagnetic resonance, nuclear magnetic resonance, and x-ray spectroscopy. Since myeloperoxidase is an central enzyme of oxygen dependent anti-microbial system of neutrophils, elucidation of the molecular mechanism of the enzyme action of myeloperoxidase is essential for our understanding the bactericidal function of polymorphonuclear leukocyte, which is vital for the survival of mammalian species against bacterial infections.