Title

Identification and Characterization of VPO1, a New Animal Heme-Containing Peroxidase

Department

Molecular & Cellular Biology

Document Type

Article

Publication Date

12-15-2008

Abstract

Animal heme-containing peroxidases play roles in innate immunity, hormone biosynthesis, and the pathogenesis of inflammatory, diseases. Using the peroxidase-like domain of Duox1 as a query, we carried out homology searching of the National Center for Biotechnology Information database. Two novel heme-containing peroxidases were identified in humans and mice. One, termed VPO1 for vascular peroxidase 1, exhibits its highest tissue expression in heart and vascular wall. A second, VPO2, present in humans but not in mice, is 63% identical to VPOI and is highly expressed in heart. The peroxidase homology region of VPOI shows 42% identity to myeloperoxidase and 57% identity to the insect peroxidase peroxidasin. A molecular model of the VPO1 peroxidase region reveals a structure very similar to that of known peroxidases, including a conserved heme binding cavity, critical catalytic residues, and a calcium binding site. The absorbance spectra of VPO1 are similar to those of lactoperoxidase, and covalent attachment of the heme to VPO1 protein was demonstrated by chemiluminescent heme staining. VPOI purified from heart or expressed in HEK cells is catalytically active, with a Km for H2O2 of 1.5 mM. When co-expressed in cells, VPOI can use H2O2 produced by NADPH oxidase enzymes. VPOI is likely to carry out peroxidative reactions previously attributed exclusively to myeloperoxidase in the vascular system.

Journal

Free Radical Biology and Medicine

Journal ISSN

0891-5849

Volume

45

Issue

12

First Page

1682

Last Page

1694

Digital Object Identifier (DOI)

10.1016/j.freeradbiomed.2008.09.009