6 , A, C, and D, and 8 A). We suggest that the metal-ion induced conformational change in PDE5 could represent an entropically driven mechanism, where the conformational entropy of the protein is altered, with no marked change in the mean structure of PDE5 ( 7 , 8 ). Indeed, divalent metal ion binding to an endonuclease was found to be largely entropy-driven without any gross structural change ( 5