色氨酸双加氧酶 (TDO) 和吲哚胺 2,3 双加氧酶 (IDO) 属于一类独特的血红素酶，它们将双氧插入必需氨基酸 L-色氨酸 (Trp) 中，生成 N-甲酰犬尿氨酸 (NFK)，犬尿氨酸途径中的关键代谢物。最近，这两种双加氧酶被认为是关键的癌症免疫治疗药物靶点，引发了大量针对它们的药物发现。然而，由于对这两种酶的结构特性以及结构决定其功能的机制了解甚少，该领域的进步受到阻碍。在这篇综述中，我们总结了以两种酶的人类亚型的结构、功能和动力学为中心的最新发现。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Tryptophan dioxygenase (TDO) and indoleamine 2,3 dioxygenase (IDO) belong to a unique class of heme-based enzymes that insert dioxygen into the essential amino acid, L-tryptophan (Trp), to generate N-formylkynurenine (NFK), a critical metabolite in the kynurenine pathway. Recently, the two dioxygenases were recognized as pivotal cancer immunotherapeutic drug targets, which triggered a great deal of drug discovery targeting them. The advancement of the field is however hampered by the poor understanding of the structural properties of the two enzymes and the mechanisms by which the structures dictate their functions. In this review, we summarize recent findings centered on the structure, function, and dynamics of the human isoforms of the two enzymes.Copyright © 2024 Elsevier Inc. All rights reserved.