Geranylgeranyltransferase type 1 explained

protein geranylgeranyltransferase type I
Ec Number:	2.5.1.59
Cas Number:	135371-29-8
Go Code:	0004662

GGTase 1 α-subunit (farnesyltransferase, CAAX box)
Hgncid:	3782
Symbol:	FNTA
Entrezgene:	2339
Omim:	134635
Refseq:	NM_002027
Uniprot:	P49354
Pdb:	1S64
Ecnumber:	2.5.1.59
Chromosome:	8
Arm:	p
Band:	11.21

GGTase 1 β-subunit (protein geranylgeranyl- transferase type I, β subunit)
Hgncid:	8895
Symbol:	PGGT1B
Entrezgene:	5229
Omim:	602031
Refseq:	NM_005023
Uniprot:	P53609
Pdb:	1S64
Ecnumber:	2.5.1.59
Chromosome:	5
Arm:	q
Band:	23.1

Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase is one of the three enzymes 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.^[1]

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, 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.^[1]

Structure

Geranylgeranyltransferase contains two subunits, 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.^{[2] [3]}

See also

• Farnesyltransferase
• Prenylation
• Rab geranylgeranyltransferase – Geranylgeranyltransferase type 2

Further reading

• Eastman RT, Buckner FS, Yokoyama K, Gelb MH, Van Voorhis WC . Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation . J. Lipid Res. . 47 . 2 . 233–40 . February 2006 . 16339110 . 10.1194/jlr.R500016-JLR200 . free .
• El Oualid F, Cohen LH, van der Marel GA, Overhand M . Inhibitors of protein: geranylgeranyl transferases . Curr. Med. Chem. . 13 . 20 . 2385–427 . 2006 . 16918362 . 10.2174/092986706777935078.

Notes and References

1. Lane KT, Beese LS . Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I . J. Lipid Res. . 47 . 4 . 681–99 . April 2006 . 16477080 . 10.1194/jlr.R600002-JLR200 . free .
2. Reid TS, Terry KL, Casey PJ, Beese LS . Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity . J. Mol. Biol. . 343 . 2 . 417–33 . October 2004 . 15451670 . 10.1016/j.jmb.2004.08.056 .
3. Long SB, Casey PJ, Beese LS . Reaction path of protein farnesyltransferase at atomic resolution . Nature . 419 . 6907 . 645–50 . October 2002 . 12374986 . 10.1038/nature00986 . 2002Natur.419..645L . 4412580 .