| 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 | ||||||||
| |||||||||
| 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 | ||||||
| |||||||
| 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 | ||||||
| |||||||
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]
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]
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]
