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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of the gene encoding alkylglycerol monooxygenase defines a third class of tetrahydrobiopterin-dependent enzymes
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Identification of the gene encoding alkylglycerol monooxygenase defines a third class of tetrahydrobiopterin-dependent enzymes

机译：编码烷基甘油单加氧酶的基因的鉴定定义了第三类四氢生物蝶呤依赖性酶

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摘要

Alkylglycerol monooxygenase (glyceryl-ether monooxygenase, EC 1.14.16.5) is the only enzyme known to cleave the O-alkyl bond of ether lipids which are essential components of brain membranes, protect the eye from cataract, interfere or mediate signalling processes, and are required for spermatogenesis. Along with phe-nylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydro-xylase, and nitric oxide synthase, alkylglycerol monooxygenase is one of five known enzymatic reactions which depend on tetra-hydrobiopterin. Although first described in 1964, no sequence had been assigned to this enzyme so far since it lost activity upon protein purification attempts. A functional library screen using pools of plasmids of a rat liver expression library transfected to CHO cells was also unsuccessful. We therefore selected human candidate genes by bioinformatic approaches and by proteomic analysis of partially purified enzyme and tested alkylglycerol monooxygenase activity in CHO cells transfected with expression plasmids. Transmembrane protein 195, a predicted membrane protein with unassigned function which occurs in bilateral animals, was found to encode for tetrahydrobiopterin-dependent alkylglycerol monooxygenase. This sequence assignment was confirmed by injection of transmembrane protein 195 cRNA into Xenopus laevis oocytes. Transmembrane protein 195 shows no sequence homology to aromatic amino acid hydroxylases or nitric oxide synthases, but contains the fatty acid hydroxylase motif. This motif is found in enzymes which contain a diiron center and which carry out hydroxylations of lipids at aliphatic carbon atoms like alkylglycerol monooxygenase. This sequence assignment suggests that alkylglycerol monooxygenase forms a distinct third group among tetrahydrobiopterin-dependent enzymes.
机译：烷基甘油单加氧酶（甘油醚单加氧酶，EC 1.14.16.5）是已知的唯一一种裂解醚脂质的O-烷基键的酶，醚脂质是脑膜的重要组成部分，可保护眼睛免受白内障，干扰或介导信号传导过程，并且是生精所必需的。与苯丙氨酸丙氨酸羟化酶，酪氨酸羟化酶，色氨酸羟化酶和一氧化氮合酶一起，烷基甘油单加氧酶是五个依赖四氢生物蝶呤的已知酶促反应之一。尽管在1964年首次进行了描述，但是到目前为止，该酶尚未分配任何序列，因为它在尝试进行蛋白质纯化时失去了活性。使用转染至CHO细胞的大鼠肝脏表达文库的质粒库进行的功能文库筛选也不成功。因此，我们通过生物信息学方法和部分纯化的酶的蛋白质组学方法选择了人类候选基因，并在用表达质粒转染的CHO细胞中测试了烷基甘油单加氧酶的活性。发现跨膜蛋白195是一种在双侧动物中发生的具有未分配功能的预测膜蛋白，其编码四氢生物蝶呤依赖性烷基甘油单加氧酶。通过将跨膜蛋白195 cRNA注射到非洲爪蟾卵母细胞中，证实了该序列分配。跨膜蛋白195与芳香族氨基酸羟化酶或一氧化氮合酶没有序列同源性，但是含有脂肪酸羟化酶基序。该基序存在于含有二价铁中心并在脂族碳原子上进行脂质羟基化的酶（如烷基甘油单加氧酶）中。该序列分配表明，烷基甘油单加氧酶在四氢生物蝶呤依赖性酶中形成独特的第三基团。

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    Katrin Watschinger; rnMarkus A. Keller; rnGeorg Golderer; rnMartin Hermann; rnManuel Maglione; rnBettina Sarg; rnHerbert H. Lindner; rnAlbin Hermetter; rnGabriele Werner-Felmayer; rnRobert Konrat; rnNicolas Hulo; rnErnst R. Werner;

  • 作者单位

    Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria;

    rnDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria;

    rnDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria;

    rnDepartment of Visceral-, Transplant-, and Thoracic Surgery, Daniel-Swarovski-Research Laboratory, Innsbruck Medical University, Innrain 66, A-6020 Innsbruck, Austria;

    rnDepartment of Visceral-, Transplant-, and Thoracic Surgery, Daniel-Swarovski-Research Laboratory, Innsbruck Medical University, Innrain 66, A-6020 Innsbruck, Austria;

    rnDivision of Clinical Biochemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria;

    rnDivision of Clinical Biochemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria;

    rnInstitute of Biochemistry, Graz University of Technology, Petersgasse 12/2, A-8010 Graz, Austria;

    rnDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria;

    rnDepartment of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter Campus 5, A-1030 Vienna, Austria;

    rnCentre Medical Universitaire and Structural Biology and Bioinformatics Department, 1 Rue Michel-Servet, CH-1211 Geneva 4, Switzerland;

    rnDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    EC 1.14.16.5; glyceryl-ether monooxygenase; nitric oxide synthase; phenylalanine hydroxylase; transmembrane protein 195;

    机译：EC 1.14.16.5;甘油醚单加氧酶;一氧化氮合酶苯丙氨酸羟化酶;跨膜蛋白195;

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