Booth Elizabeth S, Basran Jaswir, Lee Michael, Handa Sandeep, Raven Emma L
From the Department of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, Great Britain, United Kingdom and.
Department of Molecular and Cellular Biology and Henry Wellcome Laboratories for Structural Biology, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, Great Britain, United Kingdom.
J Biol Chem. 2015 Dec 25;290(52):30924-30. doi: 10.1074/jbc.M115.695684. Epub 2015 Oct 28.
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.
犬尿氨酸途径是生物学中L-色氨酸（L-Trp）分解代谢的主要途径，最终导致烟酰胺腺嘌呤二核苷酸（NAD(+)）的形成。犬尿氨酸途径的起始步骤和限速步骤涉及L-色氨酸氧化为N-甲酰犬尿氨酸。这是一个依赖氧气的过程，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出来60多年后（小竹义、正山一，1936年，《生理化学杂志》243卷，237 - 244页），该反应的机制仍未明确。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制。我们观察到在L-色氨酸、1-甲基-L-色氨酸及其他一些底物类似物的氧化过程中形成了一种瞬态中间体，被确定为化合物II（高铁）物种。这些数据与吲哚胺2,3-双加氧酶催化色氨酸及其他色氨酸类似物氧化的共同反应机制一致。
