Protein farnesyltransferase farnesyl group

In normal cells, the GDP/GTP-binding proteins, after protein synthesis, move to the cell membrane to which they become hooked by a hydrophobic farnesyl group. The y-subunit is anchored in the membrane by a post-translational modification of the C-terminal CAAX sequence (C - cystein, AA - aliphatic amino acids, X - methionine). This protein is first enzymatically farnesylated by a specific farnesyltransferase, then the AAX part is cleaved by specific proteases and finally the cystein residue is converted to a methyl ester. 

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... 

Protein farnesylation, catalyzed by protein farnesyltransferase, plays important roles in the membrane association and protein-protein interaction of a number of eukaryotic proteins. The enzyme transfers a 15-carbon farnesyl moiety from famesyl diphosphate (FPP) to the sulfhydryl group of cysteine. The activity of the enzyme was measured by CE with LIE detection, which is a powerfiil alternative to classical methods involving radiolabeled FPP." LIE detection was performed with an argon ion laser (excitation, 488 nm/emission, 520 nm). A fluorescently labeled pentapeptide that was used as substrate was clearly separated from its farnesylated form under the four CE buffer conditions investigated (e.g., 25 mM borax, 25 mM SDS, pH 9.3, uncoated capillary). The method will be of great value in studies of inhibitors of protein farnesyltransferase in vitro. 

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