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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O_2 with a nonheme diiron center
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Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O_2 with a nonheme diiron center

机译：人脱氧苏氨酸羟化酶是一种参与调节细胞生长的酶，可通过非血红素二铁中心激活O_2。

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摘要

Deoxyhypusine hydroxylase is the key enzyme in the biosynthesis of hypusine containing eukaryotic translation initiation factor 5A (eIF5A), which plays an essential role in the regulation of cell proliferation. Recombinant human deoxyhypusine hydroxylase (hDOHH) has been reported to have oxygen- and iron-dependent activity, an estimated iron/holoprotein stoichiometry of 2, and a visible band at 630 nm responsible for the blue color of the as-isolated protein. EPR, Moessbauer, and XAS spectroscopic results presented herein provide direct spectroscopic evidence that hDOHH has an antiferromagnetically coupled diiron center with histidines and carboxylates as likely ligands, as suggested by mutagenesis experiments. Resonance Raman experiments show that its blue chromophore arises from a (μ-1,2-peroxo)diiron(III) center that forms in the reaction of the reduced enzyme with O_2, so the peroxo form of hDOHH is unusually stable. Nevertheless we demonstrate that it can carry out the hydroxylation of the deoxyhypusine residue present in the elF5A substrate. Despite a lack of sequence similarity, hDOHH has a nonheme diiron active site that resembles both in structure and function those found in methane and toluene monooxygenases, bacterial and mammalian ribonu-cleotide reductases, and stearoyl acyl carrier protein Δ~9-desaturase from plants, suggesting that the oxygen-activating diiron motif is a solution arrived at by convergent evolution. Notably, hDOHH is the only example thus far of a human hydroxylase with such a diiron active site.
机译：脱氧酪氨酸羟化酶是生物合成中含有真核翻译起始因子5A（eIF5A）的关键酶，它在调节细胞增殖中起重要作用。据报道，重组人脱氧水苏氨酸羟化酶（hDOHH）具有氧和铁依赖性活性，铁/全息蛋白的化学计量比估计为2，并且在630 nm处具有可见带，该带负责分离出的蛋白质的蓝色。本文提出的EPR，Moessbauer和XAS光谱结果提供了直接的光谱证据，表明hDOHH具有反铁磁耦合的二铁中心，其组氨酸和羧酸盐可能是配体，如诱变实验所提示。共振拉曼实验表明，其蓝色发色团是由还原酶与O_2反应形成的（μ-1,2-过氧）二铁（III）中心产生的，因此hDOHH的过氧形式异常稳定。尽管如此，我们证明了它可以对elF5A底物中存在的脱氧苏氨酸残基进行羟基化。尽管缺乏序列相似性，hDOHH的非血红素二铁活性位点在结构和功能上均类似于甲烷和甲苯单加氧酶，细菌和哺乳动物核糖核酸-核苷酸还原酶以及植物中的硬脂酰基酰基载体蛋白Δ〜9-去饱和酶。这表明激活氧的二价铁基序是通过收敛演化而产生的。值得注意的是，迄今为止，hDOHH是具有这种二铁活性位点的人类羟化酶的唯一实例。

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    Van V. Vu; Joseph P. Emerson; Marlene Martinho; Yeon Sook Kim; Eckard Muenck; Myung Hee Park; Lawrence Que Jr;

  • 作者单位

    Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455;

    Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455 Department of Chemistry, Mississippi State University, Mississippi State, MS 39762;

    Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213;

    National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 Department of Dental Hygiene, Cheongju University, Cheongju, 360-764 Korea;

    Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213;

    National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892;

    Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455;

  • 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

    DOHH; peroxo intermediate; eIF5A; oxygen activation;

    机译：卫生部过氧中间体eIF5A;氧活化;

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