Protein prenylation enzyme (Prenyltransferase)

Protein prenylation enzymes catalyze the addition of isoprenyl lipid groups (farnesyl or geranylgeranyl) to specific cysteine residues located near the C-terminus of substrate proteins, typically featuring CAAX motifs. The main enzymes are farnesyltransferase (FTase), geranylgeranyltransferase type I (GGTase-I), and geranylgeranyltransferase type II (Rab geranylgeranyltransferase, GGTase-II)[1][2][5][7]. These enzymes are crucial for anchoring proteins, such as Ras, Rho, and Rab GTPases, to membranes enabling their roles in cell signaling, trafficking, and cytoskeletal regulation. Abnormal activity of these enzymes and resultant changes in prenylation patterns are implicated in tumorigenesis, Alzheimer's disease, and other conditions. Pharmacological inhibition of prenylation enzymes remains a clinically explored strategy especially in cancer, though with mixed results due to complex biology and redundancy within the signaling networks they regulate[7][4][5].

Other names

PrenyltransferaseFarnesyltransferaseGeranylgeranyltransferaseFTaseGGTaseRab geranylgeranyltransferaseCAAX-box protein modification enzyme

Inhibition of protein prenylation prevents proper membrane localization and activation of oncogenic and pathogenic proteins, including members of the Ras superfamily, reducing pathological signaling Disruption of protein membrane targeting and function, leading to loss of disease-driving protein activity