Chemistry Department is pleased to host Chemistry and Biochemistry Seminar Series, Tuesday’s at 12:10 pm. Please see Ithaca College Chemistry web page.
Guest Speaker Professor Brian Callahan Ph.D. of Binghamton University will be joining us on Tuesday, November 2nd at 12:10 pm will present:
Hedgehog protein autoprocessing: therapeutic target and biotechnology tool.
Proteins in the “hedgehog” family function as extracellular signaling factors that influence multiple developmental processes in vertebrates and invertebrates. Humans require the action of three hedgehog protein paralogues: Indian, Desert and Sonic (yes…the protein is named, Sonic Hedgehog). We study an unusual chemical transformation in the biosynthesis of hedgehog proteins, called cholesterolysis. Cholesterolysis, a form of protein autoprocessing, involves the site-specific cleavage of hedgehog by a molecule of cholesterol. Through this reaction, cholesterol becomes attached covalently to one of the departing polypeptide products. It is the cholesterylated polypeptide that holds all known extracellular signaling activity. Congenital mutations that interfere with hedgehog cholesterolysis are associated with severe developmental anomalies affecting the brain and face. Activating mutations that upregulate hedgehog signaling are linked to sporadic tumors of multiple tissues.
In this talk I will describe our recent efforts to target hedgehog protein cholesterolysis for small molecule discovery. This work has led to an unexpected class of antagonists that act allosterically to divert native cholesterolysis toward a non-physiological hydrolytic side reaction. We have called this mechanism of action, paracatalytic induction. I will also describe how my students have repurposed hedgehog cholesterolysis as a tool for protein bioconjugation. The bioconjugation studies have enabled the development of new sensor for detecting dilute nucleic acid, which we are now pursuing for SARS-CoV-2 testing, see artwork below by PhD candidate, Xiaoyu Zhang.