Protein Prenylation - The Anchor of Life
Protein prenylation is a post-translational modification that consists of the attachment of 15 or 20 carbon isoprenoids to specific cysteine residues positioned near the C-termini of proteins. In a eukaryotic cell, there are several hundred prenylated proteins including most members of the Ras superfamily and heterotrimeric G-proteins; the prenyl group serves to anchor these proteins in the membrane so that they are positioned to interact with cell surface receptors either directly or via adaptor proteins. This means that essentially all signaling processes in eukaryotic cells require the participation of prenylated proteins for everything ranging from the regulation of cell division to stem cell differentiation and development. Beyond biological significance, the critical role of prenylated proteins also makes them important targets for the design of new therapeutic agents for a variety of diseases.
Research in the Distefano Group
Works in the Distefano Group on protein prenylation is focused in two areas: Chemical Biology and Biotechnology Applications. In pursuit of those studies, members of the group perform a variety of different types of experiments including chemical synthesis, biochemistry, proteomics, cell culture and animal-based work. The goal of these works is to gain insight into protein prenylation that can be used to advance biology and develop new therapeutic approaches for a broad range of diseases including cancer, Alzheimer’s disease and infectious disease.
Research Highlights
MDD Group News
Prenylated proteins from P. falciparum (malaria) reported
In a recent article published in Scientific Reports, graduate students Kiall Suazo and Charuta Palsuledesai, in the research group of Mark Distefano, in collaboration with Chad Schaber and Dr. Audrey Odom from Washington University, describe the prenylome of P. falciparum, the causative agent of malaria.
Rapid method for quantifying prenylated proteins developed
The work of former students Josh Ochocki (now at Pfizer) and Charuta Palsuledesai (now at the University of new Mexico) performed in collaboraton with the Arriaga, Li and Wattenberg groups at the Univerrsity of Minnesota recently appeared in an article published in ACS Chemical Biology. In that paper, alkyne-containing isoprenoid analogues were used to visualize and quantify levels of prenylated proteins.
New photoremovable protecting group reported
In a recent manuscript published in Organic and Biomolecular Chemistry, Graduate student Mohsen Mahmoodi in collaboration with the Blank group describe a new coumarin-based protecting group (mBhc) that can be used for thiol caging...