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

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Jennings IG, Teh T, Kobe B

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

FEBS Lett. 2001 Jan 19;488(3):196-200.

PubMed ID

11163771 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sapropterin	Phenylalanine-4-hydroxylase	Protein	Humans	Yes	Cofactor	Details