Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I

被引:191
作者
Lane, KT [1 ]
Beese, LS [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA
关键词
prenyltransferase; isoprenoid; Ras; G protein; cancer target; drug design; farnesyltransferase inhibitor; crystal structure;
D O I
10.1194/jlr.R600002-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:681 / 699
页数:19
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