Macromolecular complex found in Homo sapiens
protein geranylgeranyltransferase type I |
---|
Identifiers |
---|
EC no. | 2.5.1.59 |
---|
CAS no. | 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 / QuickGO |
---|
Search |
---|
PMC | articles |
---|
PubMed | articles |
---|
NCBI | proteins |
---|
|
GGTase 1 α-subunit (farnesyltransferase, CAAX box) |
---|
Identifiers |
---|
Symbol | FNTA |
---|
NCBI gene | 2339 |
---|
HGNC | 3782 |
---|
OMIM | 134635 |
---|
PDB | 1S64 |
---|
RefSeq | NM_002027 |
---|
UniProt | P49354 |
---|
Other data |
---|
EC number | 2.5.1.59 |
---|
Locus | Chr. 8 p11.21 |
---|
Search for |
---|
Structures | Swiss-model |
---|
Domains | InterPro |
---|
|
GGTase 1 β-subunit (protein geranylgeranyl- transferase type I, β subunit) |
---|
Identifiers |
---|
Symbol | PGGT1B |
---|
NCBI gene | 5229 |
---|
HGNC | 8895 |
---|
OMIM | 602031 |
---|
PDB | 1S64 |
---|
RefSeq | NM_005023 |
---|
UniProt | P53609 |
---|
Other data |
---|
EC number | 2.5.1.59 |
---|
Locus | Chr. 5 q23.1 |
---|
Search for |
---|
Structures | Swiss-model |
---|
Domains | InterPro |
---|
|
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
References
- ^ 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.
- ^ 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.
- ^ 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
- 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.