Title

Kinetic analyses of Macrophage Migration Inhibitory Factor-2 (MIF-2) variants for drug discovery

Lead Author Major

Natali Hoeg

Lead Author Status

Freshman

Second Author Major

Sophia Wong

Second Author Status

Freshman

Format

Poster Presentation

Faculty Mentor Name

Georgios Pantouris

Faculty Mentor Department

Chemistry

Graduate Student Mentor Name

Andrew Parkins

Graduate Student Mentor Department

Biochemistry

Abstract/Artist Statement

Macrophage Migration Inhibitory Factor-2 (MIF-2) is a proinflamatory cytokine with a profound role in cancer survival proliferation and metastasis. Its pathological activity is related with activation of the cell surface receptor, CD74. The first selective inhibitor for MIF-2 was recently discovered and characterized using biochemical and biophysical techniques. Crystallographic analysis of the protein-inhibitor complex suggests that conformational changes at the C-terminal site of MIF-2 might be important for activation of CD74. A wild type and three C-terminal truncated variants of MIF-2 will be expressed, purified and analyzed using kinetic assays to determine whether this site is involved in activation of CD74. The novel MIF-2 inhibitor will also be employed to investigate the role of MIF-2 active site in CD74 activation. Collectively, our findings will provide insights into the mechanistic details of the MIF-2 induced activation of CD74. Ultimately, the knowledge gained from this study will provide the tools for developing a new class of highly potent and selective MIF-2 inhibitors.

Location

Virtual

Start Date

25-4-2020 1:00 PM

End Date

25-4-2020 3:00 PM

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Apr 25th, 1:00 PM Apr 25th, 3:00 PM

Kinetic analyses of Macrophage Migration Inhibitory Factor-2 (MIF-2) variants for drug discovery

Virtual

Macrophage Migration Inhibitory Factor-2 (MIF-2) is a proinflamatory cytokine with a profound role in cancer survival proliferation and metastasis. Its pathological activity is related with activation of the cell surface receptor, CD74. The first selective inhibitor for MIF-2 was recently discovered and characterized using biochemical and biophysical techniques. Crystallographic analysis of the protein-inhibitor complex suggests that conformational changes at the C-terminal site of MIF-2 might be important for activation of CD74. A wild type and three C-terminal truncated variants of MIF-2 will be expressed, purified and analyzed using kinetic assays to determine whether this site is involved in activation of CD74. The novel MIF-2 inhibitor will also be employed to investigate the role of MIF-2 active site in CD74 activation. Collectively, our findings will provide insights into the mechanistic details of the MIF-2 induced activation of CD74. Ultimately, the knowledge gained from this study will provide the tools for developing a new class of highly potent and selective MIF-2 inhibitors.