High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form

Journal Article · Wed Oct 17 00:00:00 EDT 2018 · Acta Crystallographica. Section F, Structural Biology Communications

DOI:https://doi.org/10.1107/S2053230X18012955· OSTI ID:1483087

Luo, Shukun; Xu, Ke; Xiang, Shaoyun; Chen, Jie; Chen, Chunyun; Guo, Chuangxin; Tong, Youzhi; Tong, Liang

Human indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-dependent enzyme with important roles in many cellular processes and is a potential target for drug discovery against cancer and other diseases. Crystal structures of IDO1 in complex with various inhibitors have been reported. Many of these crystals belong to the same crystal form and most of the reported structures have resolutions in the range 3.2–2.3 Å. Here, three new crystal forms of human IDO1 obtained by introducing a surface mutation, K116A/K117A, distant from the active site are reported. One of these crystal forms diffracted to 1.5 Å resolution and can be readily used for soaking experiments to determine high-resolution structures of IDO1 in complex with the substrate tryptophan or inhibitors that coordinate the heme. In addition, this mutant was used to produce crystals of a complex with an inhibitor that targets the apo form of the enzyme under the same conditions; the structure of this complex was determined at 1.7 Å resolution. Overall, this mutant represents a robust platform for determining the structures of inhibitor and substrate complexes of IDO1 at high resolution.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: INDUSTRY
• OSTI ID: 1483087
• Journal Information: Acta Crystallographica. Section F, Structural Biology Communications, Vol. 74, Issue 11; ISSN 2053-230X
• Publisher: International Union of Crystallography
• Country of Publication: United States
• Language: ENGLISH