Plasticity and therapeutic potential of cAMP and cGMP-specific phosphodiesterases in Toxoplasma gondii

Apicomplexan phosphodiesterases in cyclic nucleotide turnover: conservation, function, and therapeutic potential

“…Although these preparations are not pure, liquid chromatography with tandem mass spectrometry did not detect off-target PDE capture ( 66 , 67 ). Dual-specific PDEs include TgPDE1, 5, 6, 7, 8, 9, 10, 12, 13, and 18 ( 13 , 28 , 66 , 67 ). However, it is crucial to consider that these dual-specific PDEs may primarily degrade cGMP or cAMP in Toxoplasma .…”

“…Each life stage appears to express a unique subset of PDEs with some overlap of subset members. In tachyzoites, at least 11 PDEs are detectable at the protein level but only TgPDE1 and TgPDE2 substantially contribute to tachyzoite fitness ( 66 , 67 ). TgPDE1 and TgPDE2 regulate motility, invasion, replication, and egress in the tachyzoite lytic cycle ( 66 , 67 ) but may also serve similar or unique functions in other life stages ( Fig.…”

“…Similarly, attempts at defining PDE substrate preference using recombinantly expressed soluble PDE catalytic domain fusions were inconclusive due to weak or absent PDE activity ( 66 ). To date, only immunoprecipitation of endogenously expressed epitope-tagged PDEs from tachyzoites has been used successfully to define PDE substrate preference in vitro ( 13 , 28 , 66 , 67 ). Although these preparations are not pure, liquid chromatography with tandem mass spectrometry did not detect off-target PDE capture ( 66 , 67 ).…”

“…To date, only immunoprecipitation of endogenously expressed epitope-tagged PDEs from tachyzoites has been used successfully to define PDE substrate preference in vitro ( 13 , 28 , 66 , 67 ). Although these preparations are not pure, liquid chromatography with tandem mass spectrometry did not detect off-target PDE capture ( 66 , 67 ). Dual-specific PDEs include TgPDE1, 5, 6, 7, 8, 9, 10, 12, 13, and 18 ( 13 , 28 , 66 , 67 ).…”

“…However, it is crucial to consider that these dual-specific PDEs may primarily degrade cGMP or cAMP in Toxoplasma . For example, TgPDE1, 7, and 9 prefer cGMP to cAMP as a substrate ( 28 , 67 ). The only known cAMP-specific PDE in Toxoplasma is TgPDE2 ( 28 , 66 , 67 ).…”