From early studies an initial model of PDE, active site topography was derived. This early model can be summarized into the following steps concerning cAMP active site topography:
# cAMP substrate with its adenine and ribose moieties in an "anti" relationship
# The phosphate atom in cAMP binds to PDE active site, using an arginine residue and a water molecule, which was initially associated with Mg. A second arginine residue and the Mg may also play roles during binding and/or play roles in the next step
# S2 attack of phosphorus by HO with formation of a trigonal bipyramid transition state
# 5´-AMP is formed as an "inverted" product. Electronic charges conserve the net charge overall and across the transition state