Effects of pH and chloride concentration on the structure of myeloperoxidase studied by resonance Raman spectroscopy

摘要

Neutrophils serve in host defense against micfrobial infection. Invading microorganisms are ingested into phagosomes and the neutrophil releases antibacterial agents stored in cytoplasmic granules into the phagosome. Of the enzymes secreted from the cytoplasmic granules, the most abundant is myeloperoxidase (MPO), a major constituent of the azurophilic granule. MPO catalyzes the peroxidation of Cl~- to hypochlorous acid (HOCl) at the expense of hydrogen peroxide. The extremely bactericidal HOCl is utilized in killing the invading microorganisms. The enzymatic activity of MPO is strongly dependent on pH and the concentration of Cl~-([Cl~-]).MPO is a dimeric hemoprotein composed of identical subunits linked by a single disulfide bond. One of the characteristics of MPO is that three substituents on the tetrapyrrole ring of protoporphyrin IX are covalently linked with amino acid side chains of the protein. As a result, the heme ring of MPO is bowed from the planar structure. In this study, we have examined the effects of pH and [Cl~-] on the structure of the heme moiety of human MPO by resonance Raman spectroscopy.