Structural highlights
1n4r is a 18 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , |
| Related: | 1d8d, 1fpp, 1qbq, 1ft1, 1kzo, 1kzp, 1dce, 1n4p, 1n4q, 1n4s |
| Activity: | Protein geranylgeranyltransferase type I, with EC number 2.5.1.59 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[FNTA_RAT] Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. The alpha subunit is thought to participate in a stable complex with the substrate. The beta subunit binds the peptide substrate. Through RAC1 prenylation and activation may positively regulate neuromuscular junction development downstream of MUSK (By similarity). [PGTB1_RAT] Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Acts on the Rac1, Rac2, Rap1A and Rap1B proteins. The beta subunit is responsible for peptide-binding.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first structural information for mammalian GGTase-I, including a series of substrate and product complexes that delineate the path of the chemical reaction. These structures reveal that all protein prenyltransferases share a common reaction mechanism and identify specific residues that play a dominant role in determining prenyl group specificity. This hypothesis was confirmed by converting farnesyltransferase (15-C prenyl substrate) into GGTase-I (20-C prenyl substrate) with a single point mutation. GGTase-I discriminates against farnesyl diphosphate (FPP) at the product turnover step through the inability of a 15-C FPP to displace the 20-C prenyl-peptide product. Understanding these key features of specificity is expected to contribute to optimization of anti-cancer and anti-parasite drugs.
Structure of mammalian protein geranylgeranyltransferase type-I.,Taylor JS, Reid TS, Terry KL, Casey PJ, Beese LS EMBO J. 2003 Nov 17;22(22):5963-74. PMID:14609943[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Taylor JS, Reid TS, Terry KL, Casey PJ, Beese LS. Structure of mammalian protein geranylgeranyltransferase type-I. EMBO J. 2003 Nov 17;22(22):5963-74. PMID:14609943 doi:http://dx.doi.org/10.1093/emboj/cdg571
