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]

protein geranylgeranyltransferase type I
Identifiers
EC no.2.5.1.59
CAS no.135371-29-8
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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PMCarticles
PubMedarticles
NCBIproteins
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
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StructuresSwiss-model
DomainsInterPro
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
Search for
StructuresSwiss-model
DomainsInterPro

Function

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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

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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

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References

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  1. ^ a b 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. Bibcode:2002Natur.419..645L. doi:10.1038/nature00986. PMID 12374986. S2CID 4412580.

Further reading

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