Geranylgeranyltransferase type 1

protein
Name=protein geranylgeranyltransferase type I, beta subunit
caption=


width=
HGNCid=8895
Symbol=PGGT1B
AltSymbols=
EntrezGene=5229
OMIM=602031
RefSeq=NM_005023
UniProt=P53609
PDB=1S64
ECnumber=2.5.1.59
Chromosome=5
Arm=q
Band=23.1
LocusSupplementaryData=:"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.

References

# Reid, T. Scott, Terry, Kimberly L., Casey, Patrick J., Beese, Lorena S., (2004) Crystallographic Analysis of CaaX prenyltransferases Complexed with Substrates Defines Rules of Protein Substrate Selectivity, J. "Mol. Bio", 343, 417-433.
# Eastman, Richard T., Buckner, Frederick S., et al., (2006) Fighting parasitic disease by Blocking Protein Farnesylation, "Journal of Lipid Research", 47, 233-240.
# Beese, Lorena, S., Lane, Kimberly T. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type 1. "Journal of Lipid Research", 47, 68 –698.
# Long, Stephen B., Casey, Patrick J., Beese, Lorena S., Reaction path of protein farnesyltransferase at atomic resolution. "Nature", 419, 645-650.
# El Oualid, Farid, Cohen, Louis, H., van der Marel, Gijs A., Overhand, M., (2006) Inhibitors of Protein: Geranylgeranyl Transferases. "Curr. Med. Chem.", 13, 2385-2427.

ee also

* Prenylation
* Farnesyltransferase
* Rab geranylgeranyltransferase - Geranylgeranyltransferase type 2