Geranylgeranyltransferase type 1

Geranylgeranyltransferase type 1 (GGTase-I) is an enzyme that plays a crucial role in the post-translational modification of proteins through a process known as prenylation. This modification involves the attachment of geranylgeranyl groups to the cysteine residues of specific protein substrates, a critical step for their proper localization and function within the cell. GGTase-I is particularly important in the modification of small GTPases, which are involved in various cellular processes including signal transduction, cell growth, and differentiation.

Function

GGTase-I specifically catalyzes the transfer of a 20-carbon geranylgeranyl moiety from geranylgeranyl pyrophosphate (GGPP) to the cysteine residues at the C-terminus of target proteins in a reaction that requires the presence of a CAAX motif (where C is cysteine, A is an aliphatic amino acid, and X is any amino acid). This modification increases the hydrophobicity of the target protein, facilitating its association with cell membranes and thus influencing its activity and interactions within the cell.

Structure

The enzyme is a heterodimer composed of an alpha (α) subunit and a beta (β) subunit. The α subunit is shared with another enzyme, farnesyltransferase, while the β subunit is unique to GGTase-I. This composition is critical for the enzyme's specificity towards its substrates.

Clinical Significance

Alterations in the activity of GGTase-I have been implicated in various diseases, including cancer. The enzyme's role in modifying proteins that regulate cell growth and survival makes it a potential target for therapeutic intervention. Inhibitors of GGTase-I are being explored as anticancer agents, with the rationale that blocking the prenylation of oncogenic proteins might suppress tumor growth and progression.

Research

Research into GGTase-I has focused on understanding its substrate specificity, mechanism of action, and role in disease. Studies have also been directed towards developing specific inhibitors that can selectively target GGTase-I without affecting other enzymes involved in prenylation, aiming to minimize potential side effects.

See Also

• Prenylation
• Protein prenyltransferases
• Small GTPase
• Signal transduction