Metal ion-assisted stacking interactions and the facilitated hydrolysis of nucleoside 5'-triphosphates

Abstract: The self-association properties of the common nucleosides and nucleo-tides are summarized; if defined via their nucleobases they decrease in the order, adenine> guanine> hypoxanthine> cytosine 2 uracil. Next, some aspects of the metal ion-promoted dephosphorylation of nucleoside 5'-triphosphates (NTPs) are reviewed. It is shown that the dephosphorylation rate in the presence of Cu2 ' de-creases in the series, ATP> GTP> ITP> pyrimidine-NTPs. Similarly, addition of AMP, GMP or IMP (decreasing order of effectiveness) to a Cu2+/ATP system facilitates the dephosphorylation reaction further because one of the two ATPs in the stacked reactive intermediate, occurring in low concentration, [CU~(ATP)]~(OH>, has a structural role and this 'enzyme'-like ATP4- can be re-placed by one of the mentioned nucleoside 5'-monophosphates. These results de-monstrate how weak interactions, i.e. aromatic-ring stacking, can govern the reac-tivity of a system. Next to stacking, the purine(N7)-metal ion interaction allowing bridging and stabilization of the stack by inclusion of the phosphate group(s) is important; therefore, addition of tubercidin 5'-monophosphate ( = 7-deaza