Geranylgeranyltransferase type 1 (GGTase-I)

**Geranylgeranyltransferase type 1 (GGTase-I)** is a zinc-dependent enzyme complex composed of α and β subunits. Its main function is to catalyze the transfer of a geranylgeranyl lipid (a 20-carbon isoprenoid) to the cysteine residue of proteins containing a C-terminal CaaX motif, a process known as *geranylgeranylation*. This post-translational modification increases hydrophobicity, promoting membrane association and proper cellular localization of target proteins, most notably small GTP-binding proteins (GTPases) such as members of the Rho and Rac families, which play critical roles in signal transduction, cell proliferation, and oncogenesis[1][3][5]. GGTase-I has structural and mechanistic similarities to farnesyltransferase but is distinct in substrate specificity owing to differences in its β subunit[1][3][5]. Because aberrant prenylation contributes to cancer and possibly other diseases, GGTase-I is the subject of drug development, particularly in oncology and anti-parasitic indications[1][3]. While no GGTase-I inhibitors are yet approved for clinical use, several have shown promise in preclinical or early clinical studies[1][3][5].

Other names

Geranylgeranyltransferase IGGTase IProtein geranylgeranyltransferase type ICaaX geranylgeranyltransferase

Inhibition of protein prenylation (blocks addition of geranylgeranyl group to CaaX-motif proteins), disrupts correct localization and function of oncogenic and regulatory GTPases