Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase is one of the three

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s in the

prenyltransferase Prenyltransferases (PTs) are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to isoprenyl diphosphate syntheses (IPPSs). Prenyltransferases are a functional category and include seve ...

group. In specific terms, 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.

Function

Prenyltransferases, 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 Prenylation (also known as isoprenylation or lipidation) is the addition of hydrophobic molecules to a protein or a biomolecule. It is usually assumed that prenyl groups (3-methylbut-2-en-1-yl) facilitate attachment to cell membranes, similar to ...

, causes prenylated proteins to become membrane-associated due to the hydrophobic nature of the prenyl group. Most prenylated proteins are involved in cellular signaling, wherein membrane association is critical for function.

Structure

Geranylgeranyltransferase contains two subunits, α and β that are encoded by the ''

FNTA Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha is an enzyme that in humans is encoded by the ''FNTA'' gene. Prenyltransferases attach either a farnesyl group or a geranylgeranyl group in thioether linkage to the cyst ...

'' and '' PGGT1B'' genes, respectively. Both subunits are composed primarily of

alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

. 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 The SN2 reaction is a type of reaction mechanism that is common in organic chemistry. In this mechanism, one bond is broken and one bond is formed in a concerted way, i.e., in one step. The name SN2 refers to the Hughes-Ingold symbol of the ...

type attack on the geranylgeranyl diphosphate, displacing the diphosphate.

Function

Structure

See also

References

Further reading