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

[Image: see text] Analytical ultracentrifugation has been used to analyze the oligomeric structure of the isolated regulatory domain of phenylalanine hydroxylase. The protein exhibits a monomer–dimer equilibrium with a dissociation constant of ∼46 μM; 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 μM) stabilizes the dimer. These results suggest that dimerization of the regulatory domain of phenylalanine hydroxylase is linked to allosteric activation of the enzyme.