6dub | pdb_00006dub
Crystal structure of a methyltransferase
Structural highlights
Function[NTM1B_HUMAN] Alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes monomethylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and Pro in the Pro-Pro-Lys motif. May activate NTMT1 by priming its substrates for trimethylation.[1] Publication Abstract from PubMedalpha-N-terminal methylation of proteins is an important post-translational modification that is catalyzed by two different N-terminal methyltransferases, namely NTMT1 and NTMT2. Previous studies have suggested that NTMT1 is a tri-methyltransferase, whereas NTMT2 is a mono-methyltransferase. Here, we report the first crystal structures, to our knowledge, of NTMT2 in binary complex with S-adenosyl-L-methionine as well as in ternary complex with S-adenosyl-L-homocysteine and a substrate peptide. Our structural observations combined with biochemical studies reveal that NTMT2 is also able to di-/tri-methylate the GPKRIA peptide and di-methylate the PPKRIA peptide, otherwise it is predominantly a mono-methyltransferase. The residue N89 of NTMT2 serves as a gatekeeper residue that regulates the binding of unmethylated versus monomethylated substrate peptide. Structural comparison of NTMT1 and NTMT2 prompts us to design a N89G mutant of NTMT2 that can profoundly alter its catalytic activities and product specificities. An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2.,Dong C, Dong G, Li L, Zhu L, Tempel W, Liu Y, Huang R, Min J Commun Biol. 2018 Nov 2;1:183. doi: 10.1038/s42003-018-0196-2. eCollection 2018. PMID:30417120[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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