Geranylgeranyltransferase type 1

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protein geranylgeranyltransferase type I, beta subunit
Identifiers
Symbol	PGGT1B
HUGO	8895
Entrez	5229
OMIM	602031
RefSeq	NM_005023
UniProt	P53609
Other data
Locus	Chr. 5 q23.1

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.

1 Overview
2 Geranylgeranyltransferase structure and function
3 References
4 See also

[edit] 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.

[edit] 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.

[edit] 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.