Phenylalanine Binding Is Linked to Dimerization of the Regulatory Domain of Phenylalanine Hydroxylase

Analytical ultracentrifugation has been used to analyze the oligomeric structure of the isolated regulatory domain of phenylalanine hydroxylase. The protein exhibits a monomerdimer equilibrium with a dissociation constant of similar to 46 mu M; this value is unaffected by the removal of the 24 N-terminal residues or by phosphorylation of Ser16. In contrast, phenylalanine binding (K-d = 8 mu M) stabilizes the dimer. These results suggest that dimerization of the regulatory domain of phenylalanine hydroxylase is linked to allosteric activation of the enzyme