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

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

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Structural Biology Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Vic., Australia.


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.

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