2 UNRELATED FAMILIES OF ATP-DEPENDENT ENZYMES SHARE EXTENSIVE STRUCTURAL SIMILARITIES ABOUT THEIR COFACTOR BINDING-SITES

Two proteins, D-alanine:D-alanine ligase and cAMP-dependent protein ki nase, share a remarkable degree of structural convergence despite havi ng different three-dimensional folds and different enzymatic functions . Here we report that as many as 103 residues from 10 segments form tw o identical super-secondary structures between which the cofactor ATP is bound. The cofactor, two bound metal cations, and several water mol ecules form a large network of electrostatic and hydrophobic interacti ons common to both enzymes, and these are mediated by the similar plac ement of equivalent amino acids within the common supersecondary struc tures.