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DistefanoMD

Research Abstracts Online
January - December 2011

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University of Minnesota Twin Cities
College of Science and Engineering
Department of Chemistry

PI: Mark D. Distefano

Enzymatic Lipid Modification: Mechanism and Application

Protein prenylation is a post-translational modification that consists of the addition of C15 or C20 isoprenoid groups to a variety of proteins. Because many proteins involved in signal transduction processes contain this modification, considerable interest exists in understanding the chemistry and biology of this phenomenon. Of particular note is the observation that protein prenylation is required for the transforming activity of mutant Ras oncoproteins; inhibition of the enzyme farnesyltransferase (which catalyzes protein prenylation) arrests the growth of transformed cells in a variety of in vivo models. A number of inhibitors of this enzyme are currently in clinical trials for cancer therapy and other diseases. These researchers’ work in this area is focused in two broad directions. One direction involves the study of prenylating enzymes and how they function. Mechanistic analysis via KIE measurements and studies of specificity using isoprenoid analogues and synthetic peptides are being used to interrogate mechanism and specificity. The other direction involves the use of isoprenoid analogues to enzymatically incorporate unique functionality into proteins for subsequent modification. Computational experiments ranging from DFT calculations to protein-ligand docking play a critical role in this research.

Group Members

Daniel Abate Pella, Graduate Student
Brian S. Cornille, Undergraduate Student
Jonathan Dozier, Graduate Student
Alireza Fattahi, Research Associate
Santosh Khatwani, Research Associate
Kelly Kyro, Graduate Student
Stepan Lenevich, Graduate Student
Charuta Palsuledesai, Graduate Student
Mohammad Rashidian, Graduate Student
Min Song, Undergraduate Student