Researchers determined the structure of the Polo-like Kinase 1 (Plk1), a protein known to play a role in the progression of the cell cycle. Increased levels of Plk1 have also been associated with many cancers and are a negative prognostic indicator.
Scientists from Pfizer global R&D used Fluidigm’s Topaz screening chips to investigate multiple mutant forms of Plk1. Novel crystallization conditions for the T210V mutant Plk1 kinase domain were identified and optimized in the chips. The results enabled the growth of crystals in vapor diffusion trials, which were used in structure determination. Complexes of Plk1 with the nonhydrolyzable ATP analogue adenylylimidodiphosphate or the pyrrolo-pyrazole inhibitor PHA-680626 were solved to 2.4 and 2.1 angstroms resolution, respectively.
The research article was published in the May 22 issue of Biochemistry.