Department of Molecular and Cell Biology, Leicester Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 9HN, UK.
Department of Chemistry, Leicester Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 7RH, UK.
J Inorg Biochem. 2021 Dec;225:111604. doi: 10.1016/j.jinorgbio.2021.111604. Epub 2021 Sep 16.
The kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes - tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) - leading initially to the formation of N-formylkynurenine (NFK). In this paper, we present a crystal structure of a bacterial TDO from X. campestris in complex with l-kynurenine, the hydrolysed product of NFK. l-kynurenine is bound at the active site in a similar location to the substrate (l-Trp). Hydrogen bonding interactions with Arg117 and the heme 7-propionate anchor the l-kynurenine molecule into the pocket. A mechanism for the hydrolysis of NFK in the active site is presented.
犬尿氨酸途径是色氨酸代谢的主要途径。该途径的第一步由两种血红素依赖性加氧酶之一催化 - 色氨酸 2,3-加氧酶（TDO）和吲哚胺 2,3-加氧酶（IDO）- 最初导致 N-甲酰犬尿氨酸（NFK）的形成。在本文中，我们展示了来自 X. campestris 的细菌 TDO 与 l-犬尿氨酸（NFK 的水解产物）的复合物的晶体结构。l-犬尿氨酸结合在活性位点，位置类似于底物（l-Trp）。与 Arg117 和血红素 7-丙酸酯的氢键相互作用将 l-犬尿氨酸分子锚定在口袋中。提出了在活性位点水解 NFK 的机制。
