Catalytic and regulatory roles of divalent metal cations on the phosphoryl-transfer mechanism of ADP-dependent sugar kinases from hyperthermophilic archaea

► Here we studied the metal induced regulation of the activity in the ADP-dependent kinase family. ► We used as model two glucokinases and a phosphofructokinase from hyperthermophilic archaea. ► Kinetic experiments showed that only glucokinases are strongly inhibited by free metal. ► Molecular modeling suggests that the presence of divalent metals is key for activity and regulation. ► The metal induced inhibition is the first regulatory mechanism proposed for this protein family.