Substrate specificity of protein kinases and computational prediction of substrates
Substrate specificity of protein kinases and computational prediction of substrates
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DOI：
10.1016/j.bbapap.2005.07.036
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发表时间：
2005-12-30
影响因子：
3.2
通讯作者：
Worth, RI
中科院分区：
文献类型：
--
作者：
Kobe, B;Kampmann, T;Worth, RI
为确保信号传导的准确性，激酶必须仅作用于细胞内特定的靶点子集。理解这种底物特异性的基础对于了解单个蛋白激酶在特定细胞过程中的作用至关重要。细胞内的特异性是由激酶的“肽特异性”（对磷酸化位点周围序列的分子识别）、底物募集和磷酸酶活性共同决定的。肽特异性起着关键作用，它取决于激酶与底物之间的互补性，因而取决于它们的三维结构。用于实验鉴定激酶底物和表征特异性的方法既昂贵又费力，因此，人们正在开发计算方法以减少底物鉴定所需的实验工作量。我们讨论了蛋白激酶底物特异性的结构基础，并综述了用于获取特异性信息的实验和计算方法。(c) 2005爱思唯尔有限公司。保留所有权利。
To ensure signalling fidelity, kinases must act only on a defined subset of cellular targets. Appreciating the basis for this substrate specificity is essential for understanding the role of an individual protein kinase in a particular cellular process. The specificity in the cell is determined by a combination of "peptide specificity" of the kinase (the molecular recognition of the sequence surrounding the phosphorylation site), substrate recruitment and phosphatase activity. Peptide specificity plays a crucial role and depends on the complementarity between the kinase and the substrate and therefore on their three-dimensional structures. Methods for experimental identification of kinase substrates and characterization of specificity are expensive and laborious, therefore, computational approaches are being developed to reduce the amount of experimental work required in substrate identification. We discuss the structural basis of substrate specificity of protein kinases and review the experimental and computational methods used to obtain specificity information. (c) 2005 Elsevier B.V. All rights reserved.