Protein geranylgeranyltransferase type I (GGTase-I)

Protein geranylgeranyltransferase type I (GGTase-I) is a cytosolic enzyme that catalyzes the transfer of a 20-carbon geranylgeranyl group from geranylgeranyl diphosphate (GGPP) to a cysteine residue within the C-terminal CaaX motif of substrate proteins, most notably many regulatory GTP-binding proteins. This posttranslational modification, known as geranylgeranylation, facilitates the association of the target proteins with cellular membranes and is essential for their correct localization and function in processes such as signal transduction, proliferation, and cytoskeletal organization. GGTase-I is a heterodimeric enzyme, sharing an alpha subunit with farnesyltransferase but possessing a specific beta subunit that confers substrate specificity for GGPP over FPP. The enzyme is of significant pharmacological interest for anti-cancer and anti-parasitic drug discovery due to its role in modifying proteins critical for cell growth and oncogenesis[1][3][5].

Other names

Geranylgeranyltransferase type IGGTase-ICaaX geranylgeranyltransferaseProtein GG transferase type I

Inhibition of protein geranylgeranylation (drugs block the enzyme’s ability to transfer geranylgeranyl groups to the CaaX motif of protein substrates, impeding their membrane localization and activity, especially of signaling GTPases such as RhoA, Rac1, and others)[1][3][5]