4pk6

Crystal structure of the indoleamine 2,3-dioxygenagse 1 (IDO1) complexed with imidazothiazole derivative

spinqualitylabelsall models 4pk6, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pk6 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 3.45Å Ligands: HEM, PKL 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) is considered as a promising target for the treatment of several diseases, including neurological disorders and cancer. We report here the crystal structures of two IDO1/IDO1 inhibitor complexes, one of which shows that Amg-1 is directly bound to the heme iron of IDO1 with a clear induced fit. We also describe the identification and preliminary optimization of imidazothiazole derivatives as novel IDO1 inhibitors. Using our crystal structure information and structure-activity relationships (SAR) at the pocket-B of IDO1, we found a series of urea derivatives as potent IDO1 inhibitors and revealed that generation of an induced fit and the resulting interaction with Phe226 and Arg231 are essential for potent IDO1 inhibitory activity. The results of this study are very valuable for understanding the mechanism of IDO1 activation, which is very important for structure-based drug design (SBDD) to discover potent IDO1 inhibitors. Crystal Structures and Structure-Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors.,Tojo S, Kohno T, Tanaka T, Kamioka S, Ota Y, Ishii T, Kamimoto K, Asano S, Isobe Y ACS Med Chem Lett. 2014 Aug 21;5(10):1119-23. doi: 10.1021/ml500247w. eCollection, 2014 Oct 9. PMID:25313323 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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