Prenyltransferase
Introduction
Prenyltransferases are a group of enzymes that catalyze the transfer of prenyl groups to acceptor molecules during the process of protein prenylation. This biochemical process is vital in the post-translational modification of proteins, specifically in the attachment of either farnesyl or geranylgeranyl to the C-terminus of the protein.
Classification
Prenyltransferases are classified into two main types: farnesyltransferases (FTases) and geranylgeranyltransferases (GGTases). Each of these enzymes has a specific role in the prenylation process, transferring different prenyl groups to the protein.
Farnesyltransferase
Farnesyltransferase is an enzyme that adds a 15-carbon isoprenoid called farnesyl to the C-terminus of a protein. This modification allows the protein to anchor to cell membranes, influencing its localization and function within the cell.
Geranylgeranyltransferase
Geranylgeranyltransferase, on the other hand, attaches a 20-carbon isoprenoid known as geranylgeranyl to the protein. Similar to farnesylation, geranylgeranylation also aids in the anchoring of proteins to cell membranes.
Structure
Prenyltransferases are heterodimeric enzymes, composed of two different subunits: alpha and beta. The alpha subunit is responsible for binding the prenyl donor, while the beta subunit recognizes the C-terminal motif of the protein substrate.
Function
The primary function of prenyltransferases is to facilitate the attachment of prenyl groups to proteins. This process, known as prenylation, plays a crucial role in protein function and localization. By attaching a lipid moiety to the protein, prenylation increases the hydrophobicity of the protein, allowing it to associate with cell membranes. This membrane association is critical for the function of many proteins, including Ras proteins, which are involved in signal transduction pathways.
Role in Disease
Given their role in protein prenylation, prenyltransferases have been implicated in several diseases. For instance, mutations in prenyltransferase genes can lead to progeroid syndromes, a group of genetic disorders characterized by premature aging. Moreover, overactivity of prenyltransferases, particularly farnesyltransferase, has been associated with cancer, as it leads to the overactivation of Ras proteins, which are known to promote cell growth and proliferation.
Inhibition and Therapeutic Potential
Due to their involvement in disease, prenyltransferases have emerged as potential therapeutic targets. Inhibitors of farnesyltransferase, for instance, have been developed as potential treatments for cancer. These inhibitors work by blocking the activity of farnesyltransferase, thereby preventing the prenylation and activation of Ras proteins.