Using chemical genetics and ATP analogues to dissect protein kinase function.
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.
Elphick
Lucy M
LM
Imperial College London, Cell Cycle Lab, Division of Cell and Molecular Biology, South Kensington, London SW7 2AZ, United Kingdom.
Lee
Sarah E
SE
Gouverneur
Véronique
V
Mann
David J
DJ
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D000818:Animals; D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D011485:Protein Binding; D015202:Protein Engineering; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D000255:Adenosine Triphosphate; D011494:Protein Kinases