Projects per year
Abstract
Indoleamine 2,3-dioxygenase 1 has sparked interest as an immunotherapeutic
target in cancer research. Its structure includes a loop, named the JK-loop, that
controls the orientation of the substrate or inhibitor within the active site.
However, little has been reported about the crystal structure of this loop. In the
present work, the conformation of the JK-loop is determined for the first time in
the presence of the heme cofactor in the active site through X-ray diffraction
experiments (2.44 A ˚ resolution). Molecular-dynamics trajectories were also
obtained to provide dynamic information about the loop according to the
presence of cofactor. This new structural and dynamic information highlights the
importance of the JK-loop in confining the labile heme cofactor to the active
site.
target in cancer research. Its structure includes a loop, named the JK-loop, that
controls the orientation of the substrate or inhibitor within the active site.
However, little has been reported about the crystal structure of this loop. In the
present work, the conformation of the JK-loop is determined for the first time in
the presence of the heme cofactor in the active site through X-ray diffraction
experiments (2.44 A ˚ resolution). Molecular-dynamics trajectories were also
obtained to provide dynamic information about the loop according to the
presence of cofactor. This new structural and dynamic information highlights the
importance of the JK-loop in confining the labile heme cofactor to the active
site.
| Original language | English |
|---|---|
| Pages (from-to) | 1211-1221 |
| Journal | Acta Crystallographica Section D: Biological Crystallography |
| Volume | 76 |
| DOIs | |
| Publication status | Published - 1 Dec 2020 |
Keywords
- human indoleamine-2,3-dioxygenase-1
- tryptophan metabolism
- cancer immunotherapy
- JK-loop conformation
- Molecular Dynamics
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Dive into the research topics of 'Influence of the presence of the heme cofactor on the JK-loop structure in indoleamine-2,3-dioxygenase-1'. Together they form a unique fingerprint.Projects
- 2 Finished
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Cancer immunotherapy and dual IDO/TDO inhibitors: design, synthesis, physico-chemical and biological characterizations
Mirgaux, M. & Wouters, J.
1/10/19 → 30/09/21
Project: Research
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CÉCI – Consortium of high performance computing centers
CHAMPAGNE, B., Lazzaroni, R., Geuzaine , C., Chatelain, P. & Knaepen, B.
1/01/18 → 31/12/22
Project: Research
Equipment
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High Performance Computing Technology Platform
Benoît Champagne (Manager)
Technological Platform High Performance ComputingFacility/equipment: Technological Platform
-
Physical Chemistry and characterization(PC2)
Johan Wouters (Manager) & Carmela Aprile (Manager)
Technological Platform Physical Chemistry and characterizationFacility/equipment: Technological Platform
Datasets
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Structure of human indoleamine-2,3-dioxygenase 1 (hIDO1) with a complete JK loop
MIRGAUX, M. (Creator) & Wouters, J. (Creator), University of Namur, 16 Dec 2020
DOI: 10.2210/pdb7A62/pdb
Dataset