X-Ray Crystallographic Studies of Human Myeloperoxidase

Abstract

Myeloperoxidase (MPO) occurs in the azurophil granules of mammalian neutrophils where it catalyses the hydrogen peroxide-dependent peroxidation of chloride ion to hypochlorite[ 1], a potent antibacterial, antiviral and antifungal agent [2]. It is a member of a family of mammalian peroxidases that also includes lactoperoxidase, eosinophil peroxidase and thyroid peroxidase [3]. It is also more distantly related to the prostaglandin endoperoxide synthases [4]. So far, MPO and prostaglandin H (PGH)synthase are the only two members of this family for which X-ray crystal structures have been determined. While it has not been established that the mammalian peroxidases are homologous with plant and fungal heme-containing peroxidases, their mechanisms of catalysis are likely to be quite similar. In all heme peroxidases a histidine residue provides the proximal ligand to the heme iron and a second conserved distal histidine is essential for catalytic activity. With the exception of PGH synthase, all heme-peroxidases, for which three-dimensional structures have been determined, also contain a conserved arginine in the distal heme cavity. While mammalian, plant and fungal peroxidases all catalyze the peroxidation of iodide, MPO is the only one capable of efficient peroxidation of chloride ion.