Essential role of the N-terminal autoregulatory sequence in the regulation of phenylalanine hydroxylase

Ian G. Jennings, Trazel Teh, Bostjan Kobe

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31 Citations (Scopus)

Abstract

Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine and inhibited by its cofactor tetrahydrobiopterin (BH 4). The crystal structure of PAH revealed that the N-terminal sequence of the enzyme (residues 19-29) partially covered the enzyme active site, and suggested its involvement in regulation. We show that the protein lacking this N-terminal sequence does not require activation by phenylalanine, shows an altered structural response to phenylalanine, and is not inhibited by BH 4. Our data support the model where the N-terminal sequence of PAH acts as an intrasteric autoregulatory sequence, responsible for transmitting the effect of phenylalanine activation to the active site.

Original languageEnglish
Pages (from-to)196-200
Number of pages5
JournalFEBS Letters
Volume488
Issue number3
DOIs
Publication statusPublished - 19 Jan 2001
Externally publishedYes

Keywords

  • Allosteric regulation
  • Autoregulatory sequence
  • Intrasteric regulation
  • Mutagenesis
  • Phenylalanine hydroxylase

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