IDO1 Human, Active

IDO1 exists as a monomer and is composed of a large catalytic domain, which contains the heme group, and a small non-catalytic domain with two immunoreceptor tyrosine-based inhibition motifs (ITIMs) that regulate intracellular signaling . The enzyme catalyzes the oxidation of L-tryptophan to N-formylkynurenine, the first and rate-limiting step of the kynurenine pathway . This pathway leads to the production of several metabolites, including 3-hydroxy anthranilic acid, which have immunoprotective and immunosuppressive effects .

IDO1 is widely expressed in several lymphoid and non-lymphoid organs, including lymph nodes, spleen, tonsils, lungs, and intestine, as well as immune cells such as macrophages and dendritic cells (DCs), and endothelial cells . The activity of IDO1 is regulated at the transcriptional level, where its expression is increased by transcription factors such as NF-κB, aryl hydrocarbon receptor (AhR), and CCTF. These factors are induced by stimulation with toll-like receptor (TLR) ligands or cytokines and inhibited by hypoxia . Additionally, IDO1 activity can be inhibited at the protein level by peroxynitrite, leading to IDO1 inactivation, or by suppressor of cytokine signaling 3 (SOCS3), which binds to and targets IDO1 for proteasomal degradation .

IDO1 plays a significant role in immune regulation by modulating T-cell behavior through the catabolism of tryptophan. The enzyme’s activity leads to a local reduction in tryptophan availability and an increase in bioactive metabolites such as kynurenine, which mediate immune regulation and immune tolerance . This mechanism is involved in various pathophysiological processes, including antimicrobial and antitumor defense, neuropathology, immunoregulation, and antioxidant activity .

IDO1 has been identified as a promising therapeutic target, particularly in the context of cancer immunotherapy. The enzyme’s ability to create an immunosuppressive microenvironment by depleting tryptophan and producing immunosuppressive metabolites makes it an attractive target for therapeutic intervention . Inhibitors targeting IDO1 are being explored as potential treatments to enhance anti-tumor immunity and improve the efficacy of existing cancer therapies .

Recombinant human IDO1 is produced using various expression systems, such as Escherichia coli, to obtain a highly purified and active form of the enzyme . This recombinant protein is used in research to study the enzyme’s function, regulation, and potential therapeutic applications.