Elphick Lucy M, Lee Sarah E, Gouverneur Véronique, Mann David J
Imperial College London, Cell Cycle Lab, Division of Cell and Molecular Biology, South Kensington, London SW7 2AZ, United Kingdom.
ACS Chem Biol. 2007 May 22;2(5):299-314. doi: 10.1021/cb700027u.
Protein kinases catalyze the transfer of the gamma-phosphate of ATP to a protein substrate and thereby profoundly alter the properties of the phosphorylated protein. The identification of the substrates of protein kinases has proven to be a very difficult task because of the multitude of structurally related protein kinases present in cells, their apparent redundancy of function, and the lack of absolute specificity of small-molecule inhibitors. Here, we review approaches that utilize chemical genetics to determine the functions and substrates of protein kinases, focusing on the design of ATP analogues and protein kinase binding site mutants.
蛋白激酶催化将ATP的γ-磷酸基团转移至蛋白质底物上，从而深刻改变磷酸化蛋白质的特性。由于细胞中存在众多结构相关的蛋白激酶、其功能明显冗余以及小分子抑制剂缺乏绝对特异性，已证明鉴定蛋白激酶的底物是一项非常艰巨的任务。在此，我们综述利用化学遗传学来确定蛋白激酶功能和底物的方法，重点关注ATP类似物和蛋白激酶结合位点突变体的设计。
