2Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia
3St. Petersburg State University, 199000 St. Petersburg, Russia
4Center of Preclinical Translational Research, Almazov National Medical Research Center, 197371 St. Petersburg, Russia
5Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”, Russian Academy of Sciences, 119333 Moscow, Russia
6European Molecular Biology Laboratory (EMBL), 22607 Hamburg, Germany
7Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 119071 Moscow, Russia
8Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia
9National Research Center “Kurchatov Institute”, 123182 Moscow, Russia
# These authors contributed equally to this work.
* To whom correspondence should be addressed.
Received November 1, 2017; Revision received February 2, 2018
Macrophage migration inhibitory factor (MIF) is a key proinflammatory cytokine. Inhibitors of tautomerase activity of MIF are perspective antiinflammatory compounds. Ceruloplasmin, the copper-containing ferroxidase of blood plasma, is a noncompetitive inhibitor of tautomerase activity of MIF in the reaction with p-hydroxyphenylpyruvate. Small-angle X-ray scattering established a model of the complex formed by MIF and ceruloplasmin. Crystallographic analysis of MIF with a modified active site supports the model. The stoichiometry of 3 CP/MIF trimer complex was established using gel filtration. Conformity of novel data concerning the interaction regions in the studied proteins with previous biochemical data is discussed.
KEY WORDS: X-ray analysis, small-angle X-ray scattering, protein–protein interactions, ceruloplasmin, macrophage migration inhibitory factor