Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
J Inorg Biochem. 2024 Dec;261:112707. doi: 10.1016/j.jinorgbio.2024.112707. Epub 2024 Aug 30.
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.
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，它们将氧气插入必需氨基酸 L-色氨酸（Trp）中，生成犬尿氨酸途径中的关键代谢物 N-甲酰犬尿氨酸（NFK）。最近，这两种双加氧酶被认为是癌症免疫治疗的关键药物靶点，这引发了针对它们的大量药物发现。然而，该领域的进展受到对两种酶的结构特性以及结构决定其功能的机制的理解不足的阻碍。在这篇综述中，我们总结了最近围绕两种酶的人类同工型的结构、功能和动力学的研究结果。
