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Essential role of the N‐terminal autoregulatory sequence in the regulation of phenylalanine hydroxylase
Author(s) -
Jennings Ian G.,
Teh Trazel,
Kobe Bostjan
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02426-1
Subject(s) - tetrahydrobiopterin , phenylalanine hydroxylase , phenylalanine , enzyme , sequence (biology) , chemistry , biochemistry , active site , peptide sequence , cofactor , stereochemistry , amino acid , gene
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.