We congratulate UWM Investigator: Assistant Professor Elizabeth Liedhegner, School of Biomedical Sciences & Health Care Administration and UWM Co-Investigator: Professor Nicholas Silvaggi, Department of Chemistry & Biochemistry as the recipients of a Discovery and Innovation Grant (DIG) for their research “Understanding the role of Sterol Carrier Protein 2 (SCP-2) in lipid metabolism: toward structure-based design of SCP-2 inhibitors as tools to investigate function.”
Sterol carrier protein 2 (SCP-2) is a ubiquitous protein, homologs of which are produced in mammals, insects, yeast, bacteria, and archaea. In mammals, SCP-2 is expressed in multiple tissues including the liver, intestinal tract, and brain, where it participates in intracellular lipid trafficking and metabolism. For example, SCP-2 has been shown to be a key player in endocannabinoid signaling in the brain, and in the uptake, oxidation, and esterification of fatty acids in the liver. We are pursuing a comprehensive X-ray structural characterization of the complexes between multiple SCP-2 homologs (human, rabbit, mouse, rat, dolphin, and cow) and as many endocannabinoid, sterol, fatty acid, fatty acyl-CoA, and phospholipid/sphingolipid ligands as possible. The hydrophobic binding site of insect SCP-2 was identified long ago, but there are no structures of ligand-bound mammalian SCP-2 proteins. Answering questions about which ligands SCP-2 binds, how tightly it binds them, and what downstream effects result from these interactions will require potent SCP-2 ligands for use as probes. The eventual development of such tight-binding probes of SCP-2 will require detailed structural knowledge of how known SCP-2 ligands bind to the protein. This is a current knowledge gap in the field that we are working to fill.
Information about UWM’s Office of Research, Internal Grant Programs can be read at the following link: https://uwm.edu/officeofresearch/ords/internal-grant-programs/