IDENTIFICATION OF THE MOLECULAR TRIGGER FOR ALLOSTERIC ACTIVATION IN GLYCOGEN-PHOSPHORYLASE

Activation of protein function through phosphorylation can be mimicked by the engineering of specific metal binding sites. The addition of t wo histidine residues to glycogen phosphorylase allows enzymatic activ ation by transition metals in a cooperative and allosteric manner. Cry stal structures of the metallo-enzyme have been determined and show th at the structural transition induced upon metal binding (Ni2+) is, in part, analogous to the mode of activation of the native enzyme. The de signed metal activation site allows assignment of the structural chang es which trigger activation in this allosteric enzyme and, further, pr ovide insight into the evolutionary development of multiple activation sites.