New method of kinase crystal identification using fluorescent ligand
The RIKEN Center for Life Science Technologies has developed a new process that makes it easier to identify kinase crystals and screen new kinase inhibitors.
The small kinase inhibitor SKF86002 lacks intrinsic fluorescence, but becomes fluorescent upon binding to the ATP-binding sites of a wide variety of kinases. The co-crystals can be easily distinguished by their strong fluorescence (Figs. a, b). Moreover, the co-crystals lose their fluorescence when a compound, another kinase inhibitor, binds competitively and displaces the fluorescent SKF86002 (Figs. c, d).
This inhibitor can be a useful crystal marker, crystal stabilizer, and marker for screening new kinase inhibitors and identifying the ligand co-crystals for structural analysis. The information gained from the crystal structures of these soaked complexes can be used for structure-guided drug design studies.
The study was partly supported by the "Targeted Protein Research Program" of the Ministry of Education, Culture, Sports, Science and Technology, Japan. It was published in the journal Acta Crystallographica Section D (2014).