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首页> 外文期刊>Cell metabolism >ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase.
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ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase.

机译:ADP调节SNF1,即AMP激活的蛋白激酶的酿酒酵母同源物。

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摘要

The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK.
机译:SNF1蛋白激酶复合物在调节基因表达中起着至关重要的作用,以响应发芽酵母中的细胞外葡萄糖水平。 SNF1与哺乳动物AMP激活的蛋白激酶具有结构和功能相似性。两种激酶都通过催化亚基激活环片段内苏氨酸残基的磷酸化而被激活。在这里,我们显示了ADP是一种长期寻求的代谢产物,它通过保护酶免受Glc7(其生理相关蛋白磷酸酶)的去磷酸化作用,响应葡萄糖的限制而激活SNF1。我们还显示SNF1的调节亚基有两个ADP结合位点。较紧密的位点与NADH竞争性地结合AMP,ADP和ATP,而较弱的位点不结合NADH,但负责介导ADP对去磷酸化的保护作用。诱变实验表明,ADP防止去磷酸化的一般机制在SNF1和AMPK之间是非常保守的。

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