Abstract
The tetrahydropterin-dependent aromatic amino acid hydroxylases phenylalanine hydroxylase (PheH) and tyrosine hydroxylase (TyrH) are 75% identical in their 335 C-terminal amino acid residues (1). Deletion mutagenesis and proteolysis of the native enzymes have shown that these amino acids contain the residues responsible for catalysis (2–6). Despite these extensive identities, these enzymes differ in their substrate specificities. PheH is very specific for phenylalanine; although it can hydroxylate tryptophan to a small extent, it is unable to hydroxylate tyrosine (7,8). TyrH is able to hydroxylate phenylalanine with approximately 66% the Vmax value with tyrosine (9,10). These substrate specificities are determined by the C domains (11). The goal of the experiments described here was to identify amino acid residues responsible for these different specificities.
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References
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Daubner, S.C., Melendez, J., Fitzpatrick, P.F. (2002). Substrate Specificities of Phenylalanine and Tyrosine Hydroxylase: Role of Aspartate 425 of Tyrosine Hydroxylase. In: Milstien, S., Kapatos, G., Levine, R.A., Shane, B. (eds) Chemistry and Biology of Pteridines and Folates. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0945-5_21
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DOI: https://doi.org/10.1007/978-1-4615-0945-5_21
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