Geranylgeranyltransferase type 1

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. PMID 16477080. doi:10.1194/jlr.R600002-JLR200.
  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. PMID 15451670. doi:10.1016/j.jmb.2004.08.056.
  3. ↑ Long SB, Casey PJ, Beese LS (October 2002). "Reaction path of protein farnesyltransferase at atomic resolution". Nature. 419 (6907): 645–50. PMID 12374986. doi:10.1038/nature00986.

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. PMID 16339110. doi:10.1194/jlr.R500016-JLR200. 
  • El Oualid F, Cohen LH, van der Marel GA, Overhand M (2006). "Inhibitors of protein: geranylgeranyl transferases". Curr. Med. Chem. 13 (20): 2385–427. PMID 16918362. doi:10.2174/092986706777935078. 

See also

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.