A protein geranylgeranyltransferase from bovine brain: implications for protein prenylation specificity.
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 gamma 6 subunit 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.
Yokoyama
K
K
Department of Chemistry, University of Washington, Seattle, WA 98195.
Goodwin
G W
GW
Ghomashchi
F
F
Glomset
J A
JA
Gelb
M H
MH
D019883:Alkyl and Aryl Transferases; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D004122:Dimethylallyltranstransferase / Q000378:metabolism; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry*; D013379:Substrate Specificity; D014166:Transferases / Q000378:metabolism*
D011506:Proteins; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D004122:Dimethylallyltranstransferase