Cheng Guangjie, Salerno John C, Cao Zehong, Pagano Patrick J, Lambeth J David
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Free Radic Biol Med. 2008 Dec 15;45(12):1682-94. doi: 10.1016/j.freeradbiomed.2008.09.009. Epub 2008 Sep 23.
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 VPO1 and is highly expressed in heart. The peroxidase homology region of VPO1 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. VPO1 purified from heart or expressed in HEK cells is catalytically active, with a K(m) for H(2)O(2) of 1.5 mM. When co-expressed in cells, VPO1 can use H(2)O(2) produced by NADPH oxidase enzymes. VPO1 is likely to carry out peroxidative reactions previously attributed exclusively to myeloperoxidase in the vascular system.
动物含血红素过氧化物酶在先天免疫、激素生物合成以及炎症性疾病的发病机制中发挥作用。我们以Duox1的过氧化物酶样结构域为查询序列，对美国国立生物技术信息中心数据库进行了同源性搜索。在人和小鼠中鉴定出两种新型含血红素过氧化物酶。一种被称为血管过氧化物酶1（VPO1），在心脏和血管壁中表现出最高的组织表达。另一种是VPO2，存在于人类但不存在于小鼠中，与VPO1有63%的同源性，在心脏中高度表达。VPO1的过氧化物酶同源区域与髓过氧化物酶有42%的同源性，与昆虫过氧化物酶过氧化物酶原蛋白有57%的同源性。VPO1过氧化物酶区域的分子模型显示其结构与已知过氧化物酶非常相似，包括一个保守的血红素结合腔、关键催化残基和一个钙结合位点。VPO1的吸收光谱与乳过氧化物酶相似，化学发光血红素染色证明了血红素与VPO1蛋白的共价结合。从心脏中纯化或在HEK细胞中表达的VPO1具有催化活性，对H₂O₂的K(m)值为1.5 mM。当在细胞中共表达时，VPO1可以利用NADPH氧化酶产生的H₂O₂。VPO1可能在血管系统中进行以前仅归因于髓过氧化物酶的过氧化反应。
