Farnesyltransferase
Overview
Farnesyltransferase is an enzyme that plays a crucial role in the process of protein prenylation, a post-translational modification. This enzyme catalyzes the transfer of a farnesyl group from farnesyl pyrophosphate to a cysteine residue on a target protein. The farnesylation process is critical for the proper localization and function of many proteins, including members of the Ras protein superfamily.
Structure
Farnesyltransferase is a heterodimer, composed of two subunits: a 48-kDa α-subunit and a 46-kDa β-subunit. The α-subunit is encoded by the FNTA gene, while the β-subunit is encoded by the FNTB gene. Each subunit contributes to the formation of the active site, where the farnesylation reaction occurs. The enzyme's structure is highly conserved across species, highlighting its fundamental role in cellular function.
Function
The primary function of farnesyltransferase is to catalyze the attachment of a farnesyl group to the cysteine residue of a target protein. This process, known as farnesylation, is a type of protein prenylation. Prenylation is a post-translational modification that plays a key role in the localization and function of proteins within the cell. By adding a lipophilic farnesyl group to a protein, farnesyltransferase helps to anchor the protein to the cell membrane, allowing it to interact with other membrane-associated proteins and participate in signal transduction pathways.
Role in Disease
Mutations in the genes encoding farnesyltransferase can lead to diseases. For instance, mutations in the FNTA gene have been associated with ichthyosis, a group of skin disorders characterized by dry, scaly skin. Furthermore, the enzyme's role in prenylating proteins, such as those in the Ras superfamily, has implications for cancer. Many cancers are driven by mutations in Ras proteins, and the farnesylation of these proteins by farnesyltransferase is a critical step in their activation. Therefore, farnesyltransferase inhibitors have been explored as potential anti-cancer drugs.
Farnesyltransferase Inhibitors
Farnesyltransferase inhibitors (FTIs) are a class of drugs that inhibit the function of farnesyltransferase. These drugs prevent the enzyme from adding a farnesyl group to its target proteins, thereby blocking their ability to localize to the cell membrane and participate in signal transduction. FTIs have been investigated as potential treatments for diseases such as cancer and progeria, a rare genetic condition characterized by accelerated aging.