Journal:Acta Cryst D:S2059798320013510

Influence of the presence of the heme cofactor on the JK-loop structure in indoleamine-2,3-dioxygenase-1

Mirgaux Manon, Leherte Laurence and Wouters Johan ^[1]

Molecular Tour
The structure of a protein is intimately linked to its function. In many cases, flexible loops control the orientation of the substrate or the inhibitor within the active site. However, due to their dynamical nature, loops are difficult to refine in crystal structures, unless they are stabilized by the crystal packing. Indoleamine-2,3-dioxygenase-1 (hIDO1) is no exception to the rule. It this protein, the loop that interests us is called the JK-loop.

In the present work, the refinement of the JK-loop is obtained for the first time by X-ray diffraction experiment, thanks to its crystal packing mode. To support the X-ray observation, Molecular Dynamics trajectories are also carried out to provide a dynamical information about the loop in the presence of the cofactor. Such new structural and dynamical information highlights the importance of the JK-loop in confining the labile heme cofactor into the active site.

• .
• . This surface is important in order to support the role playing by the JK-loop.
• , close to the N-terminal part of the JK-loop, facilitating the refinement of this part of the loop.
• .

References

1. ↑ Mirgaux M, Leherte L, Wouters J. Influence of the presence of the heme cofactor on the JK-loop structure in indoleamine 2,3-dioxygenase 1. Acta Crystallogr D Struct Biol. 2020 Dec 1;76(Pt 12):1211-1221. doi:, 10.1107/S2059798320013510. Epub 2020 Nov 19. PMID:33263327 doi:http://dx.doi.org/10.1107/S2059798320013510