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