Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I

More than 100 proteins necessary for eukaryotic cell growth, differentiation, and morphology require post-translational modification by the covalent attachment of an isoprenoid lipid (prenylation). Prenylated proteins include members of the Ras, Rab, and Rho families, lamins, CENPE and CENPF, and the g subunit of many small heterotrimeric G proteins. This modification is catalyzed by the protein prenyltransferases: protein farnesyltransferase ( FTase), protein geranylgeranyltransferase type I ( GGTase-I), and GGTase-II ( or RabGGTase). In this review, we examine the structural biology of FTase and GGTase-I ( the CaaX prenyltransferases) to establish a framework for understanding the molecular basis of substrate specificity and mechanism. These enzymes have been identified in a number of species, including mammals, fungi, plants, and protists. Prenyltransferase structures include complexes that represent the major steps along the reaction path, as well as a number of complexes with clinically relevant inhibitors. Such complexes may assist in the design of inhibitors that could lead to treatments for cancer, viral infection, and a number of deadly parasitic diseases. - Lane, K. T., and L. S. Beese. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I.