Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) have an independent origin; however, they have distinctly evolved to catalyze the same reaction. In general, TDO is a single-copy gene in each metazoan species, and TDO enzymes demonstrate similar enzyme activity regardless of their biological origin. In contrast, multiple IDO paralogues are observed in many species, and they display various enzymatic properties. Similar to vertebrate IDO2, invertebrate IDOs generally show low affinity/catalytic efficiency for L-Trp. Meanwhile, two IDO isoforms from scallop (IDO-I and -III) and sponge IDOs show high L-Trp catalytic activity, which is comparable to vertebrate IDO1. Site-directed mutagenesis experiments have revealed that primarily two residues, Tyr located at the 2nd residue on the F-helix (F2nd) and His located at the 9th residue on the G-helix (G9th), are crucial for the high affinity/catalytic efficiency of these 'high performance' invertebrate IDOs. Conversely, those two amino acid substitutions (F2nd/Tyr and G9th/His) resulted in high affinity and catalytic activity in other molluscan 'low performance' IDOs. In human IDO1, G9th is Ser167, whereas the counterpart residue of G9th in human TDO is His76. Previous studies have shown that Ser167 could not be substituted by His because the human IDO1 Ser167His variant showed significantly low catalytic activity. However, this may be specific for human IDO1 because G9th/His was demonstrated to be very effective in increasing the L-Trp affinity even in vertebrate IDOs. Therefore, these findings indicate that the active sites of TDO and IDO are more similar to each other than previously expected.

中文翻译：

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后生动物色氨酸降解酶的全面比较。

色氨酸2，3-双加氧酶（TDO）和吲哚胺2，3-双加氧酶（IDO）具有独立的来源；然而，它们已经明显进化为催化相同的反应。通常，TDO是每个后生动物物种的单拷贝基因，无论其生物学起源如何，TDO酶均显示出相似的酶活性。相反，在许多物种中观察到多个IDO旁系同源物，它们显示出各种酶促性质。与脊椎动物IDO2相似，无脊椎动物IDO通常显示出对L-Trp的低亲和力/催化效率。同时，来自扇贝的两种IDO亚型（IDO-I和-III）和海绵IDO显示出较高的L-Trp催化活性，可与脊椎动物IDO1相提并论。定点诱变实验表明，主要有两个残基，Tyr位于F螺旋的第2个残基（F2nd）和His位于G螺旋的第9个残基（G9th），对于这些“高性能”无脊椎动物IDO的高亲和力/催化效率至关重要。相反，这两个氨基酸取代（F2nd / Tyr和G9th / His）导致其他软体动物“性能低下”的IDO具有较高的亲和力和催化活性。在人IDO1中，G9th为Ser167，而在人TDO中G9th的对应残基为His76。先前的研究表明，Ser167不能被His取代，因为人IDO1 Ser167His变体显示出明显较低的催化活性。但是，这可能对人类IDO1特有，因为即使在脊椎动物IDO中，G9th / His也被证明在增加L-Trp亲和力方面非常有效。所以，