Parallel evolution in two homologues of phosphorylase

Abstract

The structure of the unphosphorylated, inactive form of yeast glycogen phosphorylase has been determined to a resolution of 2.6 A. The structure is similar to the phosphorylated, active form of muscle phosphorylase in the orientations of the subunits and catalytic residues, but resembles the inactive muscle enzyme in the closed, or substrate excluding, orientation of the two domains. Part of the unique yeast amino-terminal extension of 40 residues binds near the catalytic site of the second subunit in the homodimer, preventing the domain movement required for substrate access. Phosphorylation may displace the amino terminus from the active site, allowing the domains to separate.