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

FEBS Letters

Kobe, Bostjan¹  Jennings, Ian G.¹  Teh, Trazel¹ 

[1] Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia

关键词: Allosteric regulation;    Autoregulatory sequence;    Intrasteric regulation;    Mutagenesis;    Phenylalanine hydroxylase;    6-MePH4;    6-methyl-5;    6;    7;    8-tetrahydropterin;    BH4;    6R-tetrahydrobiopterin;    IARS;    intrasteric autoregulatory sequence;    PAH;    phenylalanine hydroxylase;    PAH1–428;    PAH fragment comprising residues 1–428;    PAH30–428;    PAH fragment comprising residues 30–428;    TH;    tyrosine hydroxylase;    TPH;    tryptophan hydroxylase;   

DOI  :  10.1016/S0014-5793(00)02426-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine and inhibited by its cofactor tetrahydrobiopterin (BH₄). 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 BH₄. 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.

【 授权许可】

Unknown