Using chemical genetics and ATP analogues to dissect protein kinase function.

Journal article

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.

Authors: Elphick, L; Lee, SE; Gouverneur, V; Mann, D

• Publication status: Published
• Journal: ACS chemical biology
• Volume: 2
• Issue: 5
• Pages: 299-314
• Publication date: 2007-05-01
• DOI: 10.1021/cb700027u
• EISSN: 1554-8937
• ISSN: 1554-8929
• Language: English
• Keywords: Protein Binding; Humans; Protein Kinases; Models, Molecular; Substrate Specificity; Animals; Adenosine Triphosphate; Binding Sites; Phosphorylation; Protein Engineering; Combinatorial Chemistry Techniques