Investigation of the Substrate Specificity of Farnesyltransferase and Geranylgeranyltransferase-I
Faculty Mentor(s)
Dr. Corissa Lampear
Collaborator(s)
Dr. Carol Fierke1, Dr. Ora Schueler-Furman2 and Elia Wright1 (1Department of Biological Chemistry, University of Michigan, 2Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, Jerusalem, Israel)
Document Type
Poster
Event Date
4-11-2014
Abstract
The prenyltransferases farneysltransferase (FTase) and geranylgernayltransferase-I (GGTase-I) transfer 15-carbon and 20-carbon lipid groups, respectively, to a cysteine near the C-terminus of substrate proteins, targeting them to cellular membranes. Substrates of FTase and GGTase-I are involved in many cellular pathways, and inhibitors of the prenyltransferases are being investigated to treat diseases like cancer, parasitic infection, and progeria. In general, FTase and GGTase-I are thought to recognize a CaaX motif on substrate proteins. The CaaX motif is a cysteine residue followed by two “a” groups which are nonpolar amino acids and the “X” residue was thought to determine which enzyme recognizes it. Recent studies indicate that this model should be expanded. Therefore, I am studying the substrate specificity of the prenyltransferases FTase and GGTase-I using an in vitro peptide-based fluorescent assay. I have prepared 96-well plates with enzyme and various concentrations of substrate and measured the steady state kinetics as a function of time to refine sequence specificity of FTase and GGTase-I. This work will allow us to better predict prenyltransferase substrates in vivo and to better understand the modes of efficacy of prenyltranferase inhibitors.
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