Crystallization of Cyclic Nucleotide Phosphodiesterases
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Selective inhibitors of cyclic nucleotide phosphodiesterases (PDEs) have been widely studied as therapeutic agents for the treatment of various human diseases. Three-dimensional structures are essential for the design of highly selective inhibitors, but their availability is limited by the speed of crystallization. We describe crystallization of the catalytic domains of the unligated PDE4B2B, rolipram-bound PDE4D2, and 3-isobutyl-1-methylxanthine-bound PDE5A1 using the methods of vapor diffusion and microdialysis. We also briefly describe general methods of protein crystallization to provide a background to readers outside of the crystallographic field. Finally, we discuss detailed procedures for and pitfalls of the crystallization of PDEs, which may be valuable for crystallization of other PDE members.
