Reaction: (1) 3 S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein] = 3 S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein] (overall reaction)
(1a) S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,S)PK-[protein]
(1b) S-adenosyl-L-methionine + N-terminal-N-methyl-N-(A,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-(A,S)PK-[protein]
(1c) S-adenosyl-L-methionine + N-terminal-N,N-dimethyl-N-(A,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein]
(2) 2 S-adenosyl-L-methionine + N-terminal-PPK-[protein] = 2 S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein] (overall reaction)
(2a) S-adenosyl-L-methionine + N-terminal-PPK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-PPK-[protein]
(2b) S-adenosyl-L-methionine + N-terminal-N-methyl-N-PPK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein]
Other name(s): NMT1 (gene name); METTL11A (gene name)
Systematic name: S-adenosyl-L-methionine:N-terminal-(A,P,S)PK-[protein] methyltransferase
Comments: This enzyme methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys after the initiator L-methionine is cleaved. When the terminal amino acid is L-proline, the enzyme catalyses two successive methylations of its α-amino group. When the first amino acid is either L-alanine or L-serine, the enzyme catalyses three successive methylations. The Pro-Lys in positions 2-3 cannot be exchanged for other amino acids [1,2].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Webb, K.J., Lipson, R.S., Al-Hadid, Q., Whitelegge, J.P. and Clarke, S.G. Identification of protein N-terminal methyltransferases in yeast and humans. Biochemistry 49 (2010) 5225-5235. [PMID: 20481588]
2. Tooley, C.E., Petkowski, J.J., Muratore-Schroeder, T.L., Balsbaugh, J.L., Shabanowitz, J., Sabat, M., Minor, W., Hunt, D.F. and Macara, I.G. NRMT is an α-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Nature 466 (2010) 1125-1128. [PMID: 20668449]