STRUCTURAL STUDIES OF THE DYNAMICS OF BINDING OF MIF TO PHENYLISOTHIOCYANATE

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Abstract

The intermediate states of the macrophage migration inhibition factor (MIF) complex with phenylisothiocyanate (PITC), a covalent inhibitor of the protein under study, were studied by X-ray diffraction analysis. It has been shown that prior to covalent modification of the N-terminal proline, non-covalent binding of the inhibitor occurs at the retention site, which was discovered for the first time. The retention site was identified by using the technique of short-term infusion of a MIF crystal in a cryosolution containing a ligand, followed by instant freezing in a nitrogen jet to collect diffraction data at 100 K. A comparison of the structure with the structure obtained using the crystallization of a pre-modified protein revealed details of the dynamics of PITC binding.

About the authors

A. R Nemchinova

Shubnikov Institute of Crystallography of the Kurchatov Complex Crystallography and Photonics of the NRC "Kurchatov Institute"

Moscow, Russia

A. G Ivanova

Shubnikov Institute of Crystallography of the Kurchatov Complex Crystallography and Photonics of the NRC "Kurchatov Institute"

Moscow, Russia

A. V Sokolov

Smorodentsev Influenza Research Institute of the Russian Ministry of Health

St. Petersburg, Russia

V. R Samygina

Shubnikov Institute of Crystallography of the Kurchatov Complex Crystallography and Photonics of the NRC "Kurchatov Institute"

Email: lera@crys.ras.ru
Moscow, Russia

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