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A protein kinase switch
Genome Biology volume 1, Article number: spotlight-20000929-01 (2000)
Kinase inhibitors are plagued by a lack of specificity. Now in the 21 September Nature Bishop et al. tackle the problem by building on their earlier work, in which they modified the ATP-binding sites of Src-family tyrosine kinases to accept either nucleotide analogs or modified kinase inhibitors. In the new work the researchers mutate kinases from four distinct kinase families by replacing a bulky residue with a small residue. This change provides enough room for the binding of inhibitor analogs, which are larger than their parent inhibitors and thus do not inhibit wild-type kinases (Nature 2000, 407:395-401). The in vivo specificity is demonstrated using expression arrays. Most kinases contain a bulky residue analogous to the one mutated in this study, and thus should be amenable to the kinase-sensitization strategy.
Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.
Engineering Src family protein kinases with unnatural nucleotide specificity.
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Wells, W. A protein kinase switch. Genome Biol 1, spotlight-20000929-01 (2000) doi:10.1186/gb-spotlight-20000929-01
- Protein Kinase
- Tyrosine Kinase
- Kinase Inhibitor