Identification and characterization of VPO1, a new animal heme-containing peroxidase.
Identification and characterization of VPO1, a new animal heme-containing peroxidase.
复制标题
DOI：
10.1016/j.freeradbiomed.2008.09.009
复制
发表时间：
2008-12-15
影响因子：
7.4
通讯作者：
Lambeth, J. David
中科院分区：
文献类型：
--
作者：
Cheng, Guangjie;Salerno, John C.;Cao, Zehong;Pagano, Patrick J.;Lambeth, J. David
关键词：
动物含血红素过氧化物酶在天然免疫、激素生物合成和炎症性疾病的发病机制中发挥作用。以Duox 1的过氧化物酶样结构域为查询对象，对NCBI数据库进行同源性检索。在人类和小鼠中鉴定了两种新的含血红素的过氧化物酶。一种称为VPO 1（血管过氧化物酶1），在心脏和血管壁中显示最高的组织表达。第二种是VPO 2，存在于人类中，但不存在于小鼠中，与VPO 1有63%相同，并且在心脏中高度表达。VPO 1的过氧化物酶同源区与髓过氧化物酶（MPO）的同源性为42%，与昆虫过氧化物酶（peroxidasin）的同源性为57%。VPO 1过氧化物酶区域的分子模型显示了与已知过氧化物酶高度相似的结构，包括保守的血红素结合腔、关键催化残基和钙结合位点。VPO 1的吸收光谱类似于乳过氧化物酶，并且通过荧光血红素染色证明血红素与VPO 1蛋白的共价连接。从心脏纯化或在HEK细胞中表达的VPO 1具有催化活性，并且显示出对H2O2的Km为1.5mM。当在细胞中共表达时，VPO 1可以利用Nox酶产生的H2O2。VPO 1很可能在血管系统中进行先前专门归因于MPO的过氧化反应。
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 NCBI database. Two novel heme-containing peroxidases were identified in humans and mice. One, termed VPO1 (vascular peroxidase 1), shows 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 (MPO) and 57% identity to insect peroxidase, peroxidasin. A molecular model of VPO1 peroxidase region shows a structure that is highly similar to known peroxidases, including a conserved heme-binding cavity, critical catalytic residues, and a calcium-binding site. Absorbance spectra of VPO1 are similar to 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 and shows a Km for H2O2 of 1.5 mM. When co-expressed in cells, VPO1 can utilize H2O2 produced by Nox enzymes. VPO1 is likely to carry out peroxidative reactions in the vascular system previously attributed exclusively to MPO.
登录
查看更多内容
DOI：
10.1165/ajrcmb.22.6.3980
发表时间：
2000-06-01
影响因子：
6.4
作者：
Gerson, C;Sabater, J;Conner, GE
通讯作者：
Conner, GE
影响因子：
4.8
作者：
Cheng, GJ;Lambeth, JD
通讯作者：
Lambeth, JD
影响因子：
5.4
作者：
Akasaki, Takashi;Ohya, Yusuke;Iida, Mitsuo
通讯作者：
Iida, Mitsuo
影响因子：
4.8
作者：
Geiszt, M;Witta, J;Leto, TL
通讯作者：
Leto, TL
影响因子：
7.7
作者：
Karaulanov, EE;Böttcher, RT;Niehrs, C
通讯作者：
Niehrs, C