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

Abstract

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.

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
INDUSTRY
OSTI Identifier:
1483087
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section F, Structural Biology Communications
Additional Journal Information:
Journal Volume: 74; Journal Issue: 11; Journal ID: ISSN 2053-230X
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Luo, Shukun, Xu, Ke, Xiang, Shaoyun, Chen, Jie, Chen, Chunyun, Guo, Chuangxin, Tong, Youzhi, and Tong, Liang. High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form. United States: N. p., 2018. Web. doi:10.1107/S2053230X18012955.
Luo, Shukun, Xu, Ke, Xiang, Shaoyun, Chen, Jie, Chen, Chunyun, Guo, Chuangxin, Tong, Youzhi, & Tong, Liang. High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form. United States. doi:10.1107/S2053230X18012955.
Luo, Shukun, Xu, Ke, Xiang, Shaoyun, Chen, Jie, Chen, Chunyun, Guo, Chuangxin, Tong, Youzhi, and Tong, Liang. Wed . "High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form". United States. doi:10.1107/S2053230X18012955.
@article{osti_1483087,
title = {High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form},
author = {Luo, Shukun and Xu, Ke and Xiang, Shaoyun and Chen, Jie and Chen, Chunyun and Guo, Chuangxin and Tong, Youzhi and Tong, Liang},
abstractNote = {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.},
doi = {10.1107/S2053230X18012955},
journal = {Acta Crystallographica. Section F, Structural Biology Communications},
issn = {2053-230X},
number = 11,
volume = 74,
place = {United States},
year = {2018},
month = {10}
}