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Influence of the presence of the heme cofactor on the JK‐loop structure in indoleamine 2,3‐dioxygenase 1
Author(s) -
Mirgaux Ma,
Leherte Laurence,
Wouters Johan
Publication year - 2020
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798320013510
Subject(s) - cofactor , indoleamine 2,3 dioxygenase , heme , active site , loop (graph theory) , chemistry , stereochemistry , tryptophan , enzyme , biochemistry , mathematics , amino acid , combinatorics
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 Å 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.