Demonstration of a peroxide shunt in the tetrahydropterin-dependent aromatic amino acid monooxygenases

Jorge Alex Pavon; Paul F. Fitzpatrick

doi:10.1021/ja900128m

Demonstration of a peroxide shunt in the tetrahydropterin-dependent aromatic amino acid monooxygenases

Jorge Alex Pavon, Paul F. Fitzpatrick

Department of Biochemistry & Structural Biology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

The nonheme iron enzyme phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase catalyze the hydroxylation of their aromatic amino acid substrates using a tetrahydropterin as the source of electrons. The hydroxylating intermediate is proposed to be an Fe(IV)O species. We report here that all three enzymes will catalyze hydroxylation reactions using H ₂O ₂ in place of tetrahydropterin and oxygen, forming tyrosine and 3-hydroxyphenylalanine from phenylalanine, 4-HOCH ₂-phenylalanine from 4-CH _3- phenylalanine, and hydroxycyclohexylalanine from 3-cyclohexylalanine. No peroxide-dependent reaction is seen with active site mutants of TyrH and PheH in which the stability or reactivity of the iron center is compromised. These results provide further support for an Fe(IV)O hydroxylating intermediate.

Original language	English (US)
Pages (from-to)	4582-4583
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	131
Issue number	13
DOIs	https://doi.org/10.1021/ja900128m
State	Published - Apr 8 2009

ASJC Scopus subject areas

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

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title = "Demonstration of a peroxide shunt in the tetrahydropterin-dependent aromatic amino acid monooxygenases",

abstract = "The nonheme iron enzyme phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase catalyze the hydroxylation of their aromatic amino acid substrates using a tetrahydropterin as the source of electrons. The hydroxylating intermediate is proposed to be an Fe(IV)O species. We report here that all three enzymes will catalyze hydroxylation reactions using H 2O 2 in place of tetrahydropterin and oxygen, forming tyrosine and 3-hydroxyphenylalanine from phenylalanine, 4-HOCH 2-phenylalanine from 4-CH 3- phenylalanine, and hydroxycyclohexylalanine from 3-cyclohexylalanine. No peroxide-dependent reaction is seen with active site mutants of TyrH and PheH in which the stability or reactivity of the iron center is compromised. These results provide further support for an Fe(IV)O hydroxylating intermediate.",

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N2 - The nonheme iron enzyme phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase catalyze the hydroxylation of their aromatic amino acid substrates using a tetrahydropterin as the source of electrons. The hydroxylating intermediate is proposed to be an Fe(IV)O species. We report here that all three enzymes will catalyze hydroxylation reactions using H 2O 2 in place of tetrahydropterin and oxygen, forming tyrosine and 3-hydroxyphenylalanine from phenylalanine, 4-HOCH 2-phenylalanine from 4-CH 3- phenylalanine, and hydroxycyclohexylalanine from 3-cyclohexylalanine. No peroxide-dependent reaction is seen with active site mutants of TyrH and PheH in which the stability or reactivity of the iron center is compromised. These results provide further support for an Fe(IV)O hydroxylating intermediate.

AB - The nonheme iron enzyme phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase catalyze the hydroxylation of their aromatic amino acid substrates using a tetrahydropterin as the source of electrons. The hydroxylating intermediate is proposed to be an Fe(IV)O species. We report here that all three enzymes will catalyze hydroxylation reactions using H 2O 2 in place of tetrahydropterin and oxygen, forming tyrosine and 3-hydroxyphenylalanine from phenylalanine, 4-HOCH 2-phenylalanine from 4-CH 3- phenylalanine, and hydroxycyclohexylalanine from 3-cyclohexylalanine. No peroxide-dependent reaction is seen with active site mutants of TyrH and PheH in which the stability or reactivity of the iron center is compromised. These results provide further support for an Fe(IV)O hydroxylating intermediate.

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Demonstration of a peroxide shunt in the tetrahydropterin-dependent aromatic amino acid monooxygenases

Abstract

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