Structural Study of the Complex Formed by Ceruloplasmin and Macrophage Migration Inhibitory Factor


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Abstract

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.

About the authors

A. V. Sokolov

Institute of Experimental Medicine; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency; St. Petersburg State University; Center of Preclinical Translational Research

Email: lera@crys.ras.ru
Russian Federation, St. Petersburg, 197376; Moscow, 119435; St. Petersburg, 199000; St. Petersburg, 197371

L. A. Dadinova

Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”

Email: lera@crys.ras.ru
Russian Federation, Moscow, 119333

M. V. Petoukhov

Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”; European Molecular Biology Laboratory (EMBL); Frumkin Institute of Physical Chemistry and Electrochemistry; Semenov Institute of Chemical Physics

Email: lera@crys.ras.ru
Russian Federation, Moscow, 119333; Hamburg, 22607; Moscow, 119071; Moscow, 119991

G. Bourenkov

European Molecular Biology Laboratory (EMBL)

Email: lera@crys.ras.ru
Germany, Hamburg, 22607

K. M. Dubova

Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”

Email: lera@crys.ras.ru
Russian Federation, Moscow, 119333

S. V. Amarantov

Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”

Email: lera@crys.ras.ru
Russian Federation, Moscow, 119333

V. V. Volkov

Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”

Email: lera@crys.ras.ru
Russian Federation, Moscow, 119333

V. A. Kostevich

Institute of Experimental Medicine; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: lera@crys.ras.ru
Russian Federation, St. Petersburg, 197376; Moscow, 119435

N. P. Gorbunov

Institute of Experimental Medicine

Email: lera@crys.ras.ru
Russian Federation, St. Petersburg, 197376

N. A. Grudinina

Institute of Experimental Medicine

Email: lera@crys.ras.ru
Russian Federation, St. Petersburg, 197376

V. B. Vasilyev

Institute of Experimental Medicine; St. Petersburg State University

Email: lera@crys.ras.ru
Russian Federation, St. Petersburg, 197376; St. Petersburg, 199000

V. R. Samygina

Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”; National Research Center “Kurchatov Institute”

Author for correspondence.
Email: lera@crys.ras.ru
Russian Federation, Moscow, 119333; Moscow, 123182


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