A Protein Geranylgeranyltransferase from Bovine Brain: Implications for Protein Prenylation Specificity

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 12; pp. 5302 - 5306
• Main Authors: Yokoyama, Kohei, Goodwin, Gary W., Ghomashchi, Farideh, Glomset, John A., Gelb, Michael H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.06.1991; National Acad Sciences
• Subjects: Alkyl and Aryl Transferases; Amino Acid Sequence; Amino acids; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; brain; Brain - enzymology; Cattle; Chromatography, Gel; Chromatography, Thin Layer; Cytosol; Dimethylallyltranstransferase - metabolism; Diphosphates; Enzymes; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Lamins; Molecular Sequence Data; Platelet function tests; prenylation; protein geranylgeranyltransferase; Proteins; Proteins - chemistry; Pulmonary function tests; Substrate Specificity; Transferases; Transferases - metabolism; Ungulates; Yeasts; Brain; Molecular processing; Purification; Synthetic substrate; Bovine; Enzyme; Cytosol; Site specificity; Vertebrata; Chemical modification; Mammalia; Enzymatic activity; C terminal aminoacid; Substrate specificity; Artiodactyla; Ungulata; G protein
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.12.5302

A protein geranylgeranyltransferase (PGT) that catalyzes the transfer of a 20-carbon prenyl group from geranylgeranyl pyrophosphate to a cysteine residue in protein and peptide acceptors was detected in bovine brain cytosol and partially purified. The enzyme was shown to be distinct from a previously characterized protein farnesyltransferase (PFT). The PGT selectively geranylgeranylated a synthetic peptide corresponding to the C terminus of the γ6subunit of bovine brain G proteins, which have previously been shown to contain a 20-carbon prenyl modification. Likewise, a peptide corresponding to the C terminus of human lamin B, a known farnesylated protein, selectively served as a substrate for farnesylation by the PFT. However, with high concentrations of peptide acceptors, both prenyl transferases were able to use either peptide as substrates and the PGT was able to catalyze farnesyl transfer. Among the prenyl acceptors tested, peptides and proteins with leucine or phenylalanine at their C termini served as geranylgeranyl acceptors, whereas those with C-terminal serine were preferentially farnesylated. These results suggest that the C-terminal amino acid is an important structural determinant in controlling the specificity of protein prenylation.