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通过进化保存的伪基因酶进行蛋白质AMPylation

Anju Sreelatha1, Samantha S Yee1, Victor A Lopez1

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

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|October 2, 2018
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概括

假基因酶曾经被认为是不活跃的,可将AMP转移到蛋白质中. 蛋白-O (SelO) 具有这种AMPylation活性,对于细胞对氧化应激的反应至关重要.

关键词:
这里是SELENOO乙化葡萄糖毒素葡萄糖化激酶结构氧化应激单半氨酸

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科学领域:

  • 生物化学
  • 分子生物学
  • 细胞生物学

背景情况:

  • 蛋白激酶是关键的酶,但由于缺乏催化残留物,约10%被归类为伪激酶.
  • 伪基因酶在很大程度上被认为是催化不活的,限制了它们已知的功能作用.

研究的目的:

  • 为了研究保存的伪激酶,蛋白-O (SelO) 的功能活性.
  • 探索伪基因酶的常规激酶功能之外的潜在酶活性.

主要方法:

  • 用X射线结晶学来确定SelO活动的结构基础.
  • 在体外测试以证明AMP转移到蛋白质基质.
  • 细胞局部化研究和SelO在氧化应激反应中的作用分析.

主要成果:

  • SelO催化了AMP从ATP转移到蛋白质基板上的Ser,Thr和Tyr残留物,这一过程被称为AMPylation.
  • 晶体结构显示了类似酶的折叠与改变的ATP结合部位,解释了催化机制.
  • SelO局部化到线粒体和AMPylates调节氧化还原平衡的蛋白质,证明其在细胞防御中的作用.

结论:

  • 以Selo为例的伪基因酶具有像AMPylation这样的新型转移酶活动.
  • AMPylation是一种潜在的广泛的翻译后修饰.
  • SelO的活性对细胞适应氧化应激至关重要,突出表现为功能性酶.