Protein N-terminal methyltransferase explained

Protein N-terminal methyltransferase
Ec Number:	2.1.1.244

Protein N-terminal methyltransferase (NMT1 (gene), METTL11A (gene)) is an enzyme with systematic name S-adenosyl-L-methionine:N-terminal-(A,P,S)PK-(protein) methyltransferase.^{[1] [2]} This enzyme catalyses the following chemical reaction

(1) 3 S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein]

\rightleftharpoons 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]

\rightleftharpoons 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]

\rightleftharpoons 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-serine-[protein]

\rightleftharpoons 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]

\rightleftharpoons 2 S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein] (overall reaction)

(2a) S-adenosyl-L-methionine + N-terminal-PPK-[protein]

\rightleftharpoons S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-PPK-[protein]

(2b) S-adenosyl-L-methionine + N-terminal-N-methyl-N-PPK-[protein]

\rightleftharpoons S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein]

This enzyme methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys.

Notes and References

1. Webb KJ, Lipson RS, Al-Hadid Q, Whitelegge JP, Clarke SG . Identification of protein N-terminal methyltransferases in yeast and humans . Biochemistry . 49 . 25 . 5225–35 . June 2010 . 20481588 . 2890028 . 10.1021/bi100428x .
2. Tooley CE, Petkowski JJ, Muratore-Schroeder TL, Balsbaugh JL, Shabanowitz J, Sabat M, Minor W, Hunt DF, Macara IG . NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein . Nature . 466 . 7310 . 1125–8 . August 2010 . 20668449 . 2939154 . 10.1038/nature09343 .