Harris Todd R, Aronov Pavel A, Hammock Bruce D
Department of Entomology and Cancer Research Center, University of California, Davis, California 95616, USA.
DNA Cell Biol. 2008 Sep;27(9):467-77. doi: 10.1089/dna.2008.0751.
The mammalian soluble epoxide hydrolase (sEH) is a multidomain enzyme composed of C- and N-terminal regions that contain active sites for epoxide hydrolase (EH) and phosphatase activities, respectively. We report the cloning of two 60 kDa multidomain enzymes from the purple sea urchin Strongylocentrotus purpuratus displaying significant sequence similarity to both the N- and C-terminal domains of the mammalian sEH. While one urchin enzyme did not exhibit EH activity, the second enzyme hydrolyzed several lipid messenger molecules metabolized by the mammalian sEH, including the epoxyeicosatrienoic acids. Neither of the urchin enzymes displayed phosphatase activity. The urchin EH was inhibited by small molecule inhibitors of the mammalian sEH and is the likely ancestor of the enzyme. Sequence comparisons suggest that the urchin sEH homologs are the result of a gene fusion event between a gene encoding for an EH and a gene for an enzyme of undetermined function. This fusion event was followed by a duplication event to produce the urchin enzymes.
哺乳动物可溶性环氧化物水解酶（sEH）是一种多结构域酶，由C端和N端区域组成，分别含有环氧化物水解酶（EH）活性位点和磷酸酶活性位点。我们报告了从紫海胆（Strongylocentrotus purpuratus）中克隆出两种60 kDa的多结构域酶，它们与哺乳动物sEH的N端和C端结构域均显示出显著的序列相似性。虽然一种海胆酶未表现出EH活性，但第二种酶能水解几种由哺乳动物sEH代谢的脂质信使分子，包括环氧二十碳三烯酸。这两种海胆酶均未显示出磷酸酶活性。海胆EH受到哺乳动物sEH小分子抑制剂的抑制，它可能是该酶的祖先。序列比较表明，海胆sEH同源物是一个编码EH的基因与一个功能未明的酶基因之间发生基因融合事件的结果。该融合事件之后发生了一次复制事件，从而产生了海胆酶。
