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Journal of Lipid Research, Vol. 47, 681-699, April 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology
Thematic Review |
Thematic review series: Lipid Posttranslational Modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710
Published, JLR Papers in Press, February 13, 2006.
1 To whom correspondence should be addressed. e-mail: lsb{at}biochem.duke.edu
More than 100 proteins necessary for eukaryotic cell growth, differentiation, and morphology require posttranslational 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 
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.
Supplementary key words prenyltransferase • isoprenoid • Ras • G protein • cancer target • drug design • farnesyltransferase inhibitor • crystal structure
Abbreviations: FPP, farnesyl diphosphate; FTase, protein farnesyltransferase; FTI, farnesyltransferase inhibitor; GGPP, geranylgeranyl diphosphate; GGTase-I, geranylgeranyltransferase type I; GTI, geranylgeranyltransferase inhibitor; PDB ID, Protein Data Bank identifier
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