Abstract
Three different protein prenyltransferases catalyze the attachment of prenyl lipid anchors to a variety of eukaryotic proteins. Farnesyltransferase-inhibitor drugs have been developed as anti-cancer agents and may also be able to treat several other diseases.
Highlights
RhoB can be both farnesylated and geranylgeranylated; Prendergast and colleagues [57] have suggested that the different levels of farnesylated and geranylgeranylated RhoB in FTItreated cells compared with untreated cells could contribute to the observed effects of farnesyl transferase inhibitors (FTIs)
Substrates and functions of non-CaaX prenyltransferases The main substrates for prenylation by GGT2 are the Rab family of proteins, the largest group of small GTPases in the comment reviews reports deposited research
Given the multiplicity and heterogeneity of these effects, it is clear that they cannot be attributed to one single farnesylated protein that lacks a lipid modification because of FT inhibition; rather, alterations in the function of several proteins probably cause the observed effects, with variations depending on the cell type, disease and organism
Summary
Three different protein prenyltransferases (farnesyltransferase and geranylgeranyltransferases I and II) catalyze the attachment of prenyl lipid anchors 15 or 20 carbons long to the carboxyl termini of a variety of eukaryotic proteins. Structural superposition of the conserved (␣-␣) barrel forming one half of bacterial squalene-hopene cyclase (the enzyme that synthesizes hopanoids) [16] with the  subunit of rat FT [17] reveals correspondence of their secondary structural elements and of the parts of their active or binding sites (Figure 2) This would make sense if the different enzymes have retained common reaction mechanisms - or at least common substrate-binding characteristics - during evolution. The ␣ subunits of GGT2 in mammals and plants have an immunoglobulin-like domain between the fifth and sixth tetratricopeptide repeat, as well as leucine-rich repeats at the carboxyl terminus The functions of these additional domains in GGT2 are as yet undefined, but they are apparently not directly involved in the interaction with substrates and Rab escort proteins (see below) [18,19]. 212.4 Genome Biology 2003, Volume 4, Issue 4, Article 212 Maurer-Stroh et al
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