Identification of methionine Nalpha-acetyltransferase from Saccharomyces cerevisiae.
N alpha-Acetylation is the most frequently occurring chemical modification of the alpha-NH2 group of eukaryotic proteins and was believed until now to be catalyzed by a single N alpha-acetyltransferase. The transfer of an acetyl group from acetyl coenzyme A to the alpha-amino group of five NH2-terminal residues (serine, alanine, methionine, glycine, and threonine) in proteins accounts for approximately 95% of acetylated residues. We have found that a crude lysate from Saccharomyces cerevisiae mutant (aaa1) deficient in N alpha-acetyltransferase activity can effectively transfer an acetyl group to peptides containing NH2-terminal methionine but not to serine or alanine. This methionine N alpha-acetyltransferase has been extensively purified, and this purified enzyme can selectively transfer an acetyl group to various model peptides containing an NH2-terminal methionine residue and a penultimate aspartyl, asparaginyl, or glutamyl residue. Such specificity of N alpha-acetylation of methionine has been previously observed based on the analysis of eukaryotic protein sequences (Persson, B., Flinta, C., Heijne, G., and Jornvall, H. (1985) Eur. J. Biochem. 152, 523-527; Arfin, S.M., and Bradshaw, R. A. (1988) Biochemistry 27, 7979-7984). The indentification of this methionine N alpha-acetyltransferase provides an explanation as to why two distinct classes of N alpha-acetylated proteins exist in nature: (i) those whose initiator methionine is acetylated and (ii) those whose penultimate residue is acetylated after cleavage of the initiator methionine.
Department of Molecular Biology, Massachusetts General Hospital, Boston.
F J
FJ
Lee
L W
LW
Lin
J A
JA
Smith
D000107:Acetylation; D000123:Acetyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013379:Substrate Specificity
D000123:Acetyltransferases; C045222:methionine acetyltransferase