Protein geranylgeranyltransferase GGTase

The first step of the series of modifications involved in the processing of CAAX-type prenyl proteins occurs in the cytoplasm, catalyzed by either protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I (GGTase-I). The specificity for either of these two enzymes for the most part depends on the identity of the last amino acid X of the CAAX consensus sequence. When X is serine, cysteine, alanine, or glutamine, the 15 carbon farnesyl group is added to the cysteine catalyzed by FTase and when X is leucine, the 20 carbon geranylgeranyl group is added by... 

S, Q, A, or C, whereas GGTase-I recognizes CaaX boxes with X = L or F. Other prenylated proteins, such as the Rab proteins involved in vesicular transport, terminate in a CC, CXC, or CC(X) , 3 motif these proteins are substrates for protein geranylgeranyltransferase type II (GGTase-II) [3]. In order to be prenylated, Rab proteins must associate with Rab escort protein after geranylgeranylation, Rab escort protein delivers the prenylated Rab to membranes. 

Farnesyltransferase is a heterodimeric protein composed of an a- and a /1-sub-unit, and zinc and magnesium ions are required for its activity [7,8]. A closely related heterodimeric enzyme is geranylgeranyltransferase I (GGTase I). It also recognizes proteins with a CAAX-box when X is leucine. Both enzymes share the same a-subunit and the requirement for Zn2+ and Mg2+ but the /1-subunits are different. The similarity of these enzymes highlights the importance of selectivity of farnesyltransferase (FT)-inhibitors. 

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