Geranylgeranyltransferase type 1
Encyclopedia
Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase is one of the three enzyme
s in the prenyltransferase
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.
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, wherein membrane association is critical for function.
s, α and β that are encoded by the FNTA
and PGGT1B genes, respectively. Both subunits are composed primarily 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.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s in the prenyltransferase
Prenyltransferase
Prenyltransferases are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to prenyl diphosphate synthases....
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 modifyPosttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
proteins by adding an isoprenoid lipid called a prenyl group to the carboxyl terminus of the target protein. This process, called prenylation
Prenylation
Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...
, causes prenylated proteins to become membrane-associated due to the hydophobic nature of the prenyl group. Most prenylated proteins are involved in cellular signaling, wherein membrane association is critical for function.
Structure
Geranylgeranyltransferase contains two subunitProtein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
s, α and β that are encoded by the FNTA
FNTA
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha is an enzyme that in humans is encoded by the FNTA gene.-Interactions:FNTA has been shown to interact with TGF beta receptor 1.-Further reading:...
and PGGT1B genes, respectively. Both subunits are composed primarily of alpha helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
. 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.
See also
- PrenylationPrenylationPrenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...
- FarnesyltransferaseFarnesyltransferaseFarnesyltransferase is one of the three enzymes in the prenyltransferase group. Farnesyltransferase adds a 15-carbon isoprenoid called a farnesyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminus of a protein...
- Rab geranylgeranyltransferaseRab geranylgeranyltransferaseRab geranylgeranyltransferase also known as geranylgeranyltransferase II is one of the three prenyltransferases. It transfers two geranylgeranyl groups to the cystein at the C-terminus of Rab proteins....
- Geranylgeranyltransferase type 2