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Cdc14酸酶使用分子内伪基质基因来刺激和调节催化

Kedric L Milholland¹, Benjamin T Waddey¹, Kevin G Velázquez-Marrero¹

¹Department of Biochemistry, Purdue University, West Lafayette, Indiana, USA.

The Journal of biological chemistry

|August 9, 2024

概括

研究人员在Cdc14酸酶中发现了一种新型的"基质类催化增强剂" (SLiCE) 基因,通过模仿基质来刺激活性. 这一进化发现揭示了调节真菌和脊椎动物中酸酶功能的独特机制.

科学领域:

生物化学生化学
分子生物学分子生物学
进化生物学进化生物学

背景情况:

Cdc14酸酶与蛋白氨酸酸酶 (PTPs) 有着共同的结构和机制联系.
Cdc14酸酶对Ser-Pro位点表现出独特的基质特异性,这对于循环依赖的激酶对细胞循环调节至关重要.
在Cdc14活性部位的进化适应可能改变了正规的PTP催化循环.

研究的目的:

研究Cdc14酸酶的进化适应和调节机制.
在Cdc14酸酶中识别和描述新的调节元素.
阐明真核生物中Cdc14调节的功能和机制相似之处和差异.

主要方法:

对Saccharomyces cerevisiae Cdc14.的动态分析
序列分析和AlphaFold2结构预测的真菌和脊椎动物Cdc14的ortologs.
在人体Cdc14A和Cdc14B中保存残留物的位点定向突变发生.

主要成果:

在真菌Cdc14中发现了一种名为"基质类催化增强剂" (SLiCE) 的新型C终端基因,该基因结合了活性位点并增强了酶水解.
在真菌和脊椎动物的Cdc14基因组中,SLiCE基因中的不变的谷氨酸残留物对催化至关重要,模仿保存的PTP活性部位谷氨酸.
虽然通过类似的机制运作,但真菌和脊椎动物的SLiCE图案显示了功能性非互换性,表明了不同的活性部位适应.
鉴定出真菌SLiCE基因是调节的目标,影响Cdc14活性.

结论:

Cdc14酸酶进化了一种不寻常的刺激性伪基质基因 (SLiCE),用于增强催化活性和调节.
SLiCE 图案代表了一种保存的进化创新,在真菌和脊椎动物中具有明显的实现,突出显示了活性位点的可塑性.
调节SLiCE基因提供了一个动态控制Cdc14酸酶活性的机制.

关键词:

Cdc1414 在线阅读酶催化酶的催化作用酶动力学酶动力学酶机制的酶机制是什么酶调节酶的调节酸酶是一种酸酶.酸化的方法是:光化.伪基质是一种伪基质.结构模型是一个结构模型.

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