Geranylgeranyltransferase type 1


 * Note:Geranylgeranyltransferase may be used to refer to either Geranylgeranyltransferase type 1 or Rab geranylgeranyltransferase

Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase is one of the three enzymes in the prenyltransferase group. Specifically, Geranylgeranyltransferase (GGTase 1) adds a 20 carbon isoprenoid called a geranylgeranyl group to proteins bearing a CaaX motif: a four amino acid sequence at the carboxyl terminal of a protein. Geranylgeranyltransferase inhibitors are being investigated as anti-cancer agents.

Overview
Prenyltrasferases, including geranylgeranyltransferase, posttranslationally modify proteins by adding an isoprenoid lipid called a prenyl group to the carboxyl terminus of the target protein. This process, called prenylation, causes prenylated proteins to become membrane associated due to the hydophobic nature of the prenyl group. Most prenylated proteins are involved in cellular signaling where membrane association is critical for function.

Geranylgeranyltransferase structure and function
Geranylgeranyltransferase has two subunits Both subunits are primarily composed of alpha helices. Geranylgeranyltransferase coordinates a zinc cation on its β subunit at the lip of the active site. Geranylgeranyltransferase has a hydrophobic binding pocket for geranylgeranyl diphosphate, the lipid donor molecule. All Geranylgeranyltransferase substrates invariably have a cysteine as their fourth to last residue. This cysteine,coordinated by the zinc, engages in an SN2 type attack on the geranylgeranyl diphosphate displacing the diphosphate.