6r63

Crystal structure of indoleamine 2,3-dioxygenase 1 (IDO1) in complex with ferric heme and MMG-0358

spinqualitylabelsall models 6r63, resolution 2.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6r63 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.894Å Ligands: HEM, JTB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function I23O1_HUMAN Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen. Publication Abstract from PubMed Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging. Its implication in pathologies such as cancer and neurodegenerative diseases has stimulated the development of IDO1 inhibitors. However, negative phase III clinical trial results of the IDO1 inhibitor epacadostat in cancer immunotherapy call for a better understanding of the role and the mechanisms of IDO1 inhibition. In this work, we investigate the molecular inhibition mechanisms of four known IDO1 inhibitors and of two quinones in detail, using different experimental and computational approaches. We also determine for the first time the X-ray structure of the highly efficient 1,2,3-triazole inhibitor MMG-0358. Based on our results and a comprehensive literature overview, we propose a classification scheme for IDO1 inhibitors according to their inhibition mechanism, which will be useful for further developments in the field. Inhibition Mechanisms of Indoleamine 2,3-Dioxygenase 1 (IDO1).,Rohrig UF, Reynaud A, Majjigapu SR, Vogel P, Pojer F, Zoete V J Med Chem. 2019 Sep 26. doi: 10.1021/acs.jmedchem.9b00942. PMID:31525930 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures

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