Phosphorylation of Phenylalanine Hydroxylase Increases the Rate Constant for Formation of the Activated Conformation of the Enzyme

Crystal A. Khan, Paul F. Fitzpatrick

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Liver phenylalanine hydroxylase (PheH) is an allosteric enzyme that is activated by phenylalanine. The enzyme is also phosphorylated by protein kinase A, but the effects of phosphorylation are unclear. Recent structural studies (Meisburger et al. (2016) J. Amer. Chem. Soc. 138, 6506-6516) support a model in which activation of the enzyme involves dimerization of the regulatory domains, creating the allosteric site for phenylalanine at the dimer interface. This conformational change also results in a change in the fluorescence of the protein that can be used to monitor activation. The kinetics of activation of PheH are biphasic over a range of phenylalanine concentrations. These data are well-described by a model involving an initial equilibrium between the resting form and the activated conformation, with a value of the equilibrium constant for formation of the activated conformation, L, equal to 0.007, followed by binding of two molecules of phenylalanine. Phosphorylation increases L 10-fold by increasing the rate constant for conversion of the resting form to the activated form. The results provide functional support for the previous structural model, identify the specific effect of phosphorylation on the enzyme, and rationalize the lack of change in the protein structure upon phosphorylation.

Original languageEnglish (US)
Pages (from-to)6274-6277
Number of pages4
JournalBiochemistry
Volume57
Issue number44
DOIs
StatePublished - Nov 6 2018

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Phosphorylation of Phenylalanine Hydroxylase Increases the Rate Constant for Formation of the Activated Conformation of the Enzyme'. Together they form a unique fingerprint.

Cite this