Structure of mammalian protein geranylgeranyltransferase type-I
AUTOR(ES)
Taylor, Jeffrey S.
FONTE
Oxford University Press
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=275430Documentos Relacionados
- Optical properties of type-I and II quantum dots
- Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity
- Leprosy type-I reaction episode mimicking facial cellulitis-the importance of early diagnosis
- The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95
- Clinical and immunological consequences of human T cell leukemia virus type-I and Schistosoma mansoni co-infection