6F0A
Crystal structure of human indoleamine 2,3-dioxygenase bound to a triazole inhibitor and alanine molecule.
Summary for 6F0A
| Entry DOI | 10.2210/pdb6f0a/pdb |
| Descriptor | Indoleamine 2,3-dioxygenase 1, ~{N}-(4-chlorophenyl)-1~{H}-1,2,3-triazol-5-amine, ALANINE, ... (5 entities in total) |
| Functional Keywords | tryptophan 2 3 dioxygenase activity electron transfer activity oxidoreductase activity heme binding indoleamine 2 3 dioxygenase activity metal ion binding dioxygenase activity, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 90248.22 |
| Authors | Swan, M.K.,Latchem, M. (deposition date: 2017-11-17, release date: 2017-12-27, Last modification date: 2024-11-06) |
| Primary citation | Alexandre, J.A.C.,Swan, M.K.,Latchem, M.J.,Boyall, D.,Pollard, J.R.,Hughes, S.W.,Westcott, J. New 4-Amino-1,2,3-Triazole Inhibitors of Indoleamine 2,3-Dioxygenase Form a Long-Lived Complex with the Enzyme and Display Exquisite Cellular Potency. Chembiochem, 19:552-561, 2018 Cited by PubMed Abstract: Indoleamine-2,3 dioxygenase 1 (IDO1) has emerged as a central regulator of immune responses in both normal and disease biology. Due to its established role in promoting tumour immune escape, IDO1 has become an attractive target for cancer treatment. A novel series of highly cell potent IDO1 inhibitors based on a 4-amino-1,2,3-triazole core have been identified. Comprehensive kinetic, biochemical and structural studies demonstrate that compounds from this series have a noncompetitive kinetic mechanism of action with respect to the tryptophan substrate. In co-complex crystal structures, the compounds bind in the tryptophan pocket and make a direct ligand interaction with the haem iron of the porphyrin cofactor. It is proposed that these data can be rationalised by an ordered-binding mechanism, in which the inhibitor binds an apo form of the enzyme that is not competent to bind tryptophan. These inhibitors also form a very tight, long-lived complex with the enzyme, which partially explains their exquisite cellular potency. This novel series represents an attractive starting point for the future development of potent IDO1-targeted drugs. PubMed: 29240291DOI: 10.1002/cbic.201700560 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.26 Å) |
Structure validation
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