Direct evidence for a phenylalanine site in the regulatory domain of phenylalanine hydroxylase
نویسندگان
چکیده
منابع مشابه
Structural Features of the Regulatory ACT Domain of Phenylalanine Hydroxylase
Phenylalanine hydroxylase (PAH) catalyzes the conversion of L-Phe to L-Tyr. Defects in PAH activity, caused by mutations in the human gene, result in the autosomal recessively inherited disease hyperphenylalaninemia. PAH activity is regulated by multiple factors, including phosphorylation and ligand binding. In particular, PAH displays positive cooperativity for L-Phe, which is proposed to bind...
متن کاملPhenylalanine 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 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 (Kd = 8 μM) stabilizes the...
متن کاملMechanism of phenylalanine regulation of phenylalanine hydroxylase.
The mechanism of phenylalanine regulation of rat liver phenylalanine hydroxylase was studied. We show that phenylalanine "activates" phenylalanine hydroxylase, converting it from an inactive to active form, by binding at a true allosteric regulatory site. One phenylalanine molecule binds per enzyme subunit; it remains at this site during catalytic turnover and, while there, cannot be hydroxylat...
متن کاملPKU mutation p.G46S prevents the stereospecific binding of l‐phenylalanine to the dimer of human phenylalanine hydroxylase regulatory domain
Mammalian phenylalanine hydroxylase (PAH) has a potential allosteric regulatory binding site for l-phenylalanine (l-Phe), in addition to its catalytic site. This arrangement is supported by a crystal structure of a homodimeric truncated form of the regulatory domain of human PAH (hPAH-RD 1-118/19-118) [Patel D et al. (2016) Sci Rep doi: 10.1038/srep23748]. In this study, a fusion protein of the...
متن کاملActivation of Phenylalanine Hydroxylase by Phenylalanine Does Not Require Binding in the Active Site
Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein's regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at w...
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ژورنال
عنوان ژورنال: Archives of Biochemistry and Biophysics
سال: 2011
ISSN: 0003-9861
DOI: 10.1016/j.abb.2010.10.009