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Different partners, opposite outcomes: a new perspective of the immunobiology of indoleamine 2,3-dioxygenase.

ABSTRACT: Indoleamine 2,3-dioxygenase (IDO), a metabolic enzyme that catalyzes tryptophan conversion into kynurenines, is a crucial regulator of immunity. Altered IDO activity is often associated with pathology, including neoplasia and autoimmunity. IDO is highly expressed in dendritic cells (DCs) that exploit the enzyme's activity and the production of tryptophan catabolites to regulate immune responses by acting on several cell types, including T lymphocytes, of which they promote a regulatory phenotype. IDO also contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that, once bound by distinct molecular partners, will either promote degradation or initiate signaling activity and self-maintenance of the enzyme. We here discuss how ITIM-dependent molecular events can affect the functional plasticity of IDO by modifying the protein half-life and its enzymic and nonenzymic functions.

SUBMITTER: Orabona C

PROVIDER: S-EPMC3409287 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Different partners, opposite outcomes: a new perspective of the immunobiology of indoleamine 2,3-dioxygenase.

Orabona Ciriana C Pallotta Maria Teresa MT Grohmann Ursula U

Molecular medicine (Cambridge, Mass.) 20120718

Indoleamine 2,3-dioxygenase (IDO), a metabolic enzyme that catalyzes tryptophan conversion into kynurenines, is a crucial regulator of immunity. Altered IDO activity is often associated with pathology, including neoplasia and autoimmunity. IDO is highly expressed in dendritic cells (DCs) that exploit the enzyme's activity and the production of tryptophan catabolites to regulate immune responses by acting on several cell types, including T lymphocytes, of which they promote a regulatory phenotype ...[more]

PMID: 22481272

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Comparison study of different indoleamine-2,3 dioxygenase inhibitors from the perspective of pharmacodynamic effects.

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Substrate stereo-specificity in tryptophan dioxygenase and indoleamine 2,3-dioxygenase.

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Computational study on new natural compound inhibitors of indoleamine 2,3-dioxygenase 1.

Project description:Indoleamine 2,3-Dioxygenase (IDO), is a speed limiting enzyme that catalyzes the decomposition and metabolism of Tryptophan along Tryptophan-IDO-Kynurenine pathway [1]. Tryptophan is a necessary amino acid for activating cell growth and metabolism. Additionally, the insufficiency of Tryptophan can lead to immune system dysfunction. Raising the level of Indoleamine 2,3-Dioxygenase protein can promote stagnation and apoptosis of effector T cells [2].In contrast, the decline in the number of effect T cells naturally protects cancer cells from attack. Therefore, Indoleamine 2,3-Dioxygenase is a potential target for tumour immunotherapy, such as melanoma, ovarian cancer, lung cancer, leukaemia, and so on, especially in solid tumours [3]. In the study, we have done sets of virtual screening aided by computer techniques in order to find potentially effective inhibitors of Indoleamine 2,3-Dioxygenase. Firstly, screening based on structure was carried out by Libdock. Then, ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction were also analyzed. Molecular docking and 3D-QSAR pharmacophore generation were used to study the mechanism of these compounds and Indoleamine 2,3-Dioxygenase's binding. A molecular dynamic analysis was carried out to assess if these potential compound's binding is stable enough. According to the results of the analysis above, two potential compounds (ZINC000012495022 and ZINC000003791817) from the ZINC database were discovered to interact with Indoleamine 2,3-Dioxygenase with appropriate energy and proved to be none toxic. The study offered valuable information of Indoleamine 2,3-Dioxygenase inhibitor-based drug discovery in cancer therapy by increasing the activity of T cells and releasing immunity suppression [4, 5].

| S-EPMC7343476 | biostudies-literature

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