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