Substrate Oxidation by Indoleamine 2,3-Dioxygenase: EVIDENCE FOR A COMMON REACTION MECHANISM.
Substrate Oxidation by Indoleamine 2,3-Dioxygenase: EVIDENCE FOR A COMMON REACTION MECHANISM.
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DOI：
10.1074/jbc.m115.695684
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发表时间：
2015-12-25
期刊：
影响因子：
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通讯作者：
Raven EL
中科院分区：
文献类型：
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作者：
Booth ES;Basran J;Lee M;Handa S;Raven EL
犬尿氨酸途径是生物学中l-色氨酸（l-Trp）催化的主要途径，最终导致NAD+的形成。犬尿氨酸途径的初始和限速步骤涉及1-Trp氧化为N-甲酰犬尿氨酸。这是一个O2依赖的过程，由吲哚胺2，3-双加氧酶和色氨酸2，3-双加氧酶催化。在这些双加氧酶首次分离后60多年（Kotake，Y.，和Masayama，I.（1936）Z. Physiol.Chem.243，237-244），反应的机理没有建立。我们研究了吲哚胺2，3-双加氧酶对一系列取代色氨酸类似物的底物氧化机理。我们观察到的瞬态中间体的形成，指定为化合物II（铁）的物种，在氧化的L-Trp，1-甲基-L-Trp，和一些其他底物类似物。这些数据与吲哚胺2，3-双加氧酶催化色氨酸和其他色氨酸类似物氧化的常见反应机理一致。
The kynurenine pathway is the major route of l-tryptophan (l-Trp) catabolism in biology, leading ultimately to the formation of NAD+. The initial and rate-limiting step of the kynurenine pathway involves oxidation of l-Trp to N-formylkynurenine. This is an O2-dependent process and catalyzed by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase. More than 60 years after these dioxygenase enzymes were first isolated (Kotake, Y., and Masayama, I. (1936) Z. Physiol. Chem. 243, 237–244), the mechanism of the reaction is not established. We examined the mechanism of substrate oxidation for a series of substituted tryptophan analogues by indoleamine 2,3-dioxygenase. We observed formation of a transient intermediate, assigned as a Compound II (ferryl) species, during oxidation of l-Trp, 1-methyl-l-Trp, and a number of other substrate analogues. The data are consistent with a common reaction mechanism for indoleamine 2,3-dioxygenase-catalyzed oxidation of tryptophan and other tryptophan analogues.