Divalent Metal Cation Requirement and Possible Classification of cGMP-Inhibited Phosphodiesterase as a Metallohydrolase

cGMP-inhibited phosphodiesterase (cGI-PDE) has been found to require a divalent metal cation for cAMP hydrolysis. The cGI-PDE isolated from human platelets exhibited significantly higher enzymatic activity when incubated with Mn2+, Mg2+, and Co2+. The addition of Zn2+, Cd2+, Ca2+, K+, or Na+to the enzyme did not enhance the activity and, when present in high concentration (>1.0 μM), Zn2+and Cd2+inhibited the enzymatic activity of cGI-PDE. The inhibition by Zn2+(and Cd2+) was partially prevented by preincubation of the enzyme with Mn2+. The enzyme was also inhibited by metal chelators EDTA and 1,10-phenanthroline and not by their non-metal-chelating analogs. The partial protection against chelation (and inhibition) was afforded by AMP (the product of cAMP hydrolysis).