构象熵在蛋白激酶 A 催化亚基的活性和调节中的作用。
Role of conformational entropy in the activity and regulation of the catalytic subunit of protein kinase A.
机构信息
Department of Biochemistry, Biophysics & Molecular Biology, University of Minnesota, Jackson Hall, MN, USA; Department of Chemistry, University of Minnesota, Smith Hall, MN, USA.
出版信息
FEBS J. 2013 Nov;280(22):5608-15. doi: 10.1111/febs.12462. Epub 2013 Aug 27.
Abstract
Protein kinase A (PKA) is the archetypical phosphokinase, sharing a catalytic core with the entire protein kinase superfamily. In eukaryotes, the ubiquitous location of PKA makes it one of the most important cellular signaling molecules, involved in a myriad of events. The catalytic subunit of PKA (PKA-C) is one of the most studied enzymes and was the first kinase to be crystallized; however, the effects of ligand binding, post-translational modifications and mutations on the activity of the kinase have been difficult to understand with only structural data. Here, we review our latest NMR studies on PKA-C, the results of which underscore the role of fast and slow conformational dynamics in the activation and inhibition of the kinase.
摘要
蛋白激酶 A（PKA）是典型的磷酸激酶，与整个蛋白激酶超家族共享一个催化核心。在真核生物中，PKA 的普遍存在使其成为最重要的细胞信号分子之一，参与了无数的事件。PKA 的催化亚基（PKA-C）是研究最多的酶之一，也是第一个被结晶的激酶；然而，仅从结构数据很难理解配体结合、翻译后修饰和突变对激酶活性的影响。在这里，我们回顾了我们最近关于 PKA-C 的 NMR 研究，研究结果强调了快速和缓慢构象动力学在激酶的激活和抑制中的作用。
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