RGD Reference Report - Structure of mammalian protein geranylgeranyltransferase type-I. - Rat Genome Database

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Structure of mammalian protein geranylgeranyltransferase type-I.

Authors: Taylor, JS  Reid, TS  Terry, KL  Casey, PJ  Beese, LS 
Citation: Taylor JS, etal., EMBO J. 2003 Nov 17;22(22):5963-74.
RGD ID: 8554040
Pubmed: (View Article at PubMed) PMID:14609943
DOI: Full-text: DOI:10.1093/emboj/cdg571

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.


Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Fnta  (farnesyltransferase, CAAX box, alpha)
Pggt1b  (protein geranylgeranyltransferase type I subunit beta)

Additional Information