Geranylgeranyltransferase type 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]

Geranylgeranyltransferase may be used to refer to either Geranylgeranyltransferase type 1 or Rab geranylgeranyltransferase
protein geranylgeranyltransferase type I
Identifiers
EC number2.5.1.59
CAS number135371-29-8
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
GGTase 1 α-subunit (farnesyltransferase, CAAX box)
Identifiers
SymbolFNTA
NCBI gene2339
HGNC3782
OMIM134635
PDB1S64
RefSeqNM_002027
UniProtP49354
Other data
EC number2.5.1.59
LocusChr. 8 p11.21
GGTase 1 β-subunit
(protein geranylgeranyl- transferase type I, β subunit)
Identifiers
SymbolPGGT1B
NCBI gene5229
HGNC8895
OMIM602031
PDB1S64
RefSeqNM_005023
UniProtP53609
Other data
EC number2.5.1.59
LocusChr. 5 q23.1

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

References
  1. 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. S2CID 4412580.

Further reading


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