四氢生物蝶呤依赖性芳香族氨基酸单加氧酶中过氧化物分流的证明。
Demonstration of a peroxide shunt in the tetrahydropterin-dependent aromatic amino acid monooxygenases.
作者信息
Pavon Jorge Alex, Fitzpatrick Paul F
机构信息
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
出版信息
J Am Chem Soc. 2009 Apr 8;131(13):4582-3. doi: 10.1021/ja900128m.
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(2)O(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.
摘要
非血红素铁酶苯丙氨酸羟化酶、酪氨酸羟化酶和色氨酸羟化酶利用四氢生物蝶呤作为电子来源，催化其芳香族氨基酸底物的羟化反应。据推测，羟化中间体是一种Fe(IV)O物种。我们在此报告，所有这三种酶都将使用过氧化氢代替四氢生物蝶呤和氧气催化羟化反应，由苯丙氨酸生成酪氨酸和3-羟基苯丙氨酸，由4-甲基苯丙氨酸生成4-羟甲基苯丙氨酸，由3-环己基丙氨酸生成羟基环己基丙氨酸。在酪氨酸羟化酶（TyrH）和苯丙氨酸羟化酶（PheH）的活性位点突变体中未观察到过氧化物依赖性反应，这些突变体中铁中心的稳定性或反应性受到损害。这些结果为Fe(IV)O羟化中间体提供了进一步的支持。
相似文献
1
Demonstration of a peroxide shunt in the tetrahydropterin-dependent aromatic amino acid monooxygenases.四氢生物蝶呤依赖性芳香族氨基酸单加氧酶中过氧化物分流的证明。
J Am Chem Soc. 2009 Apr 8;131(13):4582-3. doi: 10.1021/ja900128m.
2
Insights into the catalytic mechanisms of phenylalanine and tryptophan hydroxylase from kinetic isotope effects on aromatic hydroxylation.从芳香族羟基化的动力学同位素效应洞察苯丙氨酸和色氨酸羟化酶的催化机制。
Biochemistry. 2006 Sep 12;45(36):11030-7. doi: 10.1021/bi0607554.
3
Mechanisms of tryptophan and tyrosine hydroxylase.色氨酸和酪氨酸羟化酶的作用机制。
IUBMB Life. 2013 Apr;65(4):350-7. doi: 10.1002/iub.1144. Epub 2013 Feb 26.
4
Mutagenesis of a specificity-determining residue in tyrosine hydroxylase establishes that the enzyme is a robust phenylalanine hydroxylase but a fragile tyrosine hydroxylase.将酪氨酸羟化酶的一个决定特异性的残基进行突变，证明该酶是一种强有力的苯丙氨酸羟化酶，但却是一种脆弱的酪氨酸羟化酶。
Biochemistry. 2013 Feb 26;52(8):1446-55. doi: 10.1021/bi400031n. Epub 2013 Feb 13.
5
Biochemical and biophysical approaches to characterization of the aromatic amino acid hydroxylases.芳香族氨基酸羟化酶的生化和生物物理特性分析方法。
Methods Enzymol. 2024;704:345-361. doi: 10.1016/bs.mie.2024.05.009. Epub 2024 Jun 5.
6
A flexible loop in tyrosine hydroxylase controls coupling of amino acid hydroxylation to tetrahydropterin oxidation.酪氨酸羟化酶中的一个柔性环控制着氨基酸羟化与四氢生物蝶呤氧化的偶联。
J Mol Biol. 2006 Jun 2;359(2):299-307. doi: 10.1016/j.jmb.2006.03.016. Epub 2006 Mar 24.
7
The aromatic amino acid hydroxylases.芳香族氨基酸羟化酶
Adv Enzymol Relat Areas Mol Biol. 2000;74:235-94. doi: 10.1002/9780470123201.ch6.
8
Pulsed EPR study of amino acid and tetrahydropterin binding in a tyrosine hydroxylase nitric oxide complex: evidence for substrate rearrangements in the formation of the oxygen-reactive complex.脉冲电子顺磁共振研究酪氨酸羟化酶一氧化氮复合物中氨基酸和四氢喋呤的结合：含氧反应复合物形成中底物重排的证据。
Biochemistry. 2013 Nov 26;52(47):8430-41. doi: 10.1021/bi4010914. Epub 2013 Nov 14.
9
Evidence for a high-spin Fe(IV) species in the catalytic cycle of a bacterial phenylalanine hydroxylase.细菌苯丙氨酸羟化酶催化循环中高自旋 Fe(IV)物种的证据。
Biochemistry. 2011 Mar 22;50(11):1928-33. doi: 10.1021/bi1019868. Epub 2011 Feb 16.
10
Mechanism of "uncoupled" tetrahydropterin oxidation by phenylalanine hydroxylase.苯丙氨酸羟化酶催化“解偶联”四氢蝶呤氧化的机制。
Biochemistry. 1985 Oct 8;24(21):5839-46. doi: 10.1021/bi00342a022.
引用本文的文献
1
Dioxygen activation by nonheme iron enzymes with the 2-His-1-carboxylate facial triad that generate high-valent oxoiron oxidants.具有2-组氨酸-1-羧酸盐面三联体的非血红素铁酶对双氧的活化作用，该三联体可生成高价氧铁氧化剂。
J Biol Inorg Chem. 2017 Apr;22(2-3):339-365. doi: 10.1007/s00775-016-1431-2. Epub 2017 Jan 10.
2
Mechanisms of tryptophan and tyrosine hydroxylase.色氨酸和酪氨酸羟化酶的作用机制。
IUBMB Life. 2013 Apr;65(4):350-7. doi: 10.1002/iub.1144. Epub 2013 Feb 26.
3
Theoretical study of the mechanism of oxoiron(IV) formation from H2O2 and a nonheme iron(II) complex: O-O cleavage involving proton-coupled electron transfer.双氧水分子与非血红素铁(II)配合物生成氧代铁(IV)的反应机制的理论研究：涉及质子耦合电子转移的 O-O 键断裂。
Inorg Chem. 2011 Jul 18;50(14):6637-48. doi: 10.1021/ic200522r. Epub 2011 Jun 16.
4
Evidence for a high-spin Fe(IV) species in the catalytic cycle of a bacterial phenylalanine hydroxylase.细菌苯丙氨酸羟化酶催化循环中高自旋 Fe(IV)物种的证据。
Biochemistry. 2011 Mar 22;50(11):1928-33. doi: 10.1021/bi1019868. Epub 2011 Feb 16.
5
Single turnover kinetics of tryptophan hydroxylase: evidence for a new intermediate in the reaction of the aromatic amino acid hydroxylases.色氨酸羟化酶的单转换动力学：芳香族氨基酸羟化酶反应中新中间产物的证据。
Biochemistry. 2010 Sep 7;49(35):7563-71. doi: 10.1021/bi100744r.
本文引用的文献
1
Direct spectroscopic evidence for a high-spin Fe(IV) intermediate in tyrosine hydroxylase.酪氨酸羟化酶中高自旋Fe(IV)中间体的直接光谱证据。
J Am Chem Soc. 2007 Sep 19;129(37):11334-5. doi: 10.1021/ja074446s. Epub 2007 Aug 23.
2
Hydrogen peroxide dependent cis-dihydroxylation of benzoate by fully oxidized benzoate 1,2-dioxygenase.完全氧化的苯甲酸1,2-双加氧酶催化的过氧化氢依赖性苯甲酸顺式二羟基化反应。
Biochemistry. 2007 Jul 10;46(27):8004-16. doi: 10.1021/bi700120j. Epub 2007 Jun 14.
3
Non-heme Fe(IV)-oxo intermediates.非血红素铁（IV）-氧中间体
Acc Chem Res. 2007 Jul;40(7):484-92. doi: 10.1021/ar700066p. Epub 2007 Jun 2.
4
Insights into the catalytic mechanisms of phenylalanine and tryptophan hydroxylase from kinetic isotope effects on aromatic hydroxylation.从芳香族羟基化的动力学同位素效应洞察苯丙氨酸和色氨酸羟化酶的催化机制。
Biochemistry. 2006 Sep 12;45(36):11030-7. doi: 10.1021/bi0607554.
5
Stalking intermediates in oxygen activation by iron enzymes: motivation and method.追踪铁酶激活氧过程中的中间体：动机与方法
J Inorg Biochem. 2006 Apr;100(4):586-605. doi: 10.1016/j.jinorgbio.2006.01.022. Epub 2006 Mar 2.
6
Intrinsic isotope effects on benzylic hydroxylation by the aromatic amino acid hydroxylases: evidence for hydrogen tunneling, coupled motion, and similar reactivities.芳香族氨基酸羟化酶对苄基羟基化的内在同位素效应：氢隧穿、耦合运动和相似反应性的证据
J Am Chem Soc. 2005 Nov 30;127(47):16414-5. doi: 10.1021/ja0562651.
7
Mechanism of aromatic amino acid hydroxylation.芳香族氨基酸羟基化的机制。
Biochemistry. 2003 Dec 9;42(48):14083-91. doi: 10.1021/bi035656u.
8
Hydrogen peroxide-coupled cis-diol formation catalyzed by naphthalene 1,2-dioxygenase.萘1,2-双加氧酶催化的过氧化氢偶联顺式二醇形成反应。
J Biol Chem. 2003 Jan 10;278(2):829-35. doi: 10.1074/jbc.M209604200. Epub 2002 Oct 25.
9
Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin.人色氨酸羟化酶的三维结构及其对神经递质血清素和褪黑素生物合成的影响。
Biochemistry. 2002 Oct 22;41(42):12569-74. doi: 10.1021/bi026561f.
10
Pterin-Dependent Amino Acid Hydroxylases.蝶呤依赖性氨基酸羟化酶
Chem Rev. 1996 Nov 7;96(7):2659-2756. doi: 10.1021/cr9402034.
Zotero 插件