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Hydrolysis of the non-canonical cyclic nucleotide cUMP by PDE9A: kinetics and binding mode

Scharrenbroich, Jessica ; Kaever, Volkhard ; Dove, Stefan ; Seifert, Roland ; Schneider, Erich H.



Abstract

The non-canonical cyclic nucleotide cUMP and the phosphodiesterase PDE9A both occur in neuronal cells. Using HPLC-coupled tandem mass spectrometry, we characterized the kinetics of PDE9A-mediated cUMP hydrolysis. PDE9A is a low-affinity and high-velocity enzyme for cUMP (V-max=6mol/min/mg; K-m=401M). The PDE9 inhibitor BAY 73-6691 inhibited PDE9A-catalyzed cUMP hydrolysis (K-i=590nM). Docking ...

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