Geranylgeranyltransferase type 1

Geranylgeranyltransferase may be used to refer to either Geranylgeranyltransferase type 1 or Rab geranylgeranyltransferase
protein geranylgeranyltransferase type I
Identifiers
EC number 2.5.1.59
CAS number 135371-29-8
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
GGTase 1 α-subunit (farnesyltransferase, CAAX box)
Identifiers
Symbol FNTA
Entrez 2339
HUGO 3782
OMIM 134635
PDB 1S64
RefSeq NM_002027
UniProt P49354
Other data
EC number 2.5.1.59
Locus Chr. 8 p11.21
GGTase 1 β-subunit
(protein geranylgeranyl- transferase type I, β subunit)
Identifiers
Symbol PGGT1B
Entrez 5229
HUGO 8895
OMIM 602031
PDB 1S64
RefSeq NM_005023
UniProt P53609
Other data
EC number 2.5.1.59
Locus Chr. 5 q23.1

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 hydophobic 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]

References

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

Further reading

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

See also

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