VPO1 and VPO2: identification and characterization of two new heme‐containing peroxidases

Abstract

Heme‐containing peroxidases play diversified roles in innate immunity, synthesis of thyroid hormone and pathogenesis of inflammatory diseases. Based on the recent discovery of new ROS‐generating Nox enzymes, and the known relationship between classical Nox enzymes and peroxidases, we hypothesized the existence of novel peroxidases. Using Duox1 peroxidase domain, we carried out homology searching of the NCBI databases. Two novel heme‐containing peroxidases were identified in humans and mice. One shows highest tissue expression in heart and vascular wall, and is termed VPO1 (vascular peroxidase 1). A second, VPO2, present in humans but not in mice, is 63% identical to VPO1, and is most highly expressed in heart. VPO1 and VPO2 show 42% and 38% identity to myeloperoxidase (MPO), respectively. A molecular model of the peroxidase region of VPO1 shows a structure that is highly similar to other peroxidases, including a conserved heme‐binding cavity, critical catalytic residues, and a calcium‐binding site. Absorbance spectra of VPO1 are similar to lactoperoxidase. VPO1 purified from heart or expressed in HEK cells is catalytically active. When co‐expressed in cells, VPO1 can utilize H2O2 produced by Nox enzymes. VPO1 may carry out peroxidative reactions in the vascular system previously attributed exclusively to MPO. This work was supported by the AHA grant 0635122N and NIH grant CA105116.