Structural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase

Horne, J., Jennings, I. G., Teh, T., Gooley, P. R. and Kobe, B. (2002) Structural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase. Protein Science, 11 8: 2041-2047. doi:10.1110/ps.4560102

Author Horne, J.
Jennings, I. G.
Teh, T.
Gooley, P. R.
Kobe, B.
Title Structural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase
Journal name Protein Science   Check publisher's open access policy
ISSN 0961-8368
Publication date 2002
Sub-type Article (original research)
DOI 10.1110/ps.4560102
Open Access Status
Volume 11
Issue 8
Start page 2041
End page 2047
Total pages 7
Place of publication Plainview
Publisher Cold Spring Harbor Laboratory Press
Collection year 2002
Language eng
Subject C1
270108 Enzymes
780105 Biological sciences
Abstract Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine, and through phosphorylation by cAMP-dependent protein kinase at Ser 16 in the N-terminal autoregulatory sequence of the enzyme. The crystal structures of phosphorylated and unphosphorylated forms of the enzyme showed that, in the absence of phenylalanine, in both cases the N-terminal 18 residues including the phosphorylation site contained no interpretable electron density. We used nuclear magnetic resonance (NMR) spectroscopy to characterize this N-terminal region of the molecule in different stages of the regulatory pathway. A number of sharp resonances are observed in PAH with an intact N-terminal region, but no sharp resonances are present in a truncation mutant lacking the N-terminal 29 residues. The N-terminal sequence therefore represents a mobile flexible region of the molecule. The resonances become weaker after the addition of phenylalanine, indicating a loss of mobility. The peptides corresponding to residues 2-20 of PAH have different structural characteristics in the phosphorylated and unphosphorylated forms, with the former showing increased secondary structure. Our results support the model whereby upon phenylalanine binding, the mobile N-terminal 18 residues of PAH associate with the folded core of the molecule; phosphorylation may facilitate this interaction.
Keyword Biochemistry & Molecular Biology
Autoregulatory Sequence
Nuclear Magnetic Resonance (nmr)
Phenylalanine Hydroxylase
Amino-acid Hydroxylases
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
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Created: Tue, 14 Aug 2007, 17:22:34 EST