ArticleCommunications biology2018
An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2.
Article in Communications biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- N-terminal modifications as fate switches in neurodegeneration: a mechanistic review.Frontiers in aging neuroscience · 2026Review
- Decoding the protein methylome: Identification, validation, and functional insights.Bioorganic & medicinal chemistry · 2025Review
- Characterizations of Protein Arginine Deiminase 1 as a Substrate of NTMT1: Implications of Nα-Methylation in Protein Stability and Interaction.Journal of proteome research · 2024Article
- Structural basis of tRNA recognition by the mNature structural & molecular biology · 2024Article
- Article
- Structure-Activity Relationship Studies of Venglustat on NTMT1 Inhibition.Journal of medicinal chemistry · 2023Article
- Three's a crowd - why did three N-terminal methyltransferases evolve for one job?Journal of cell science · 2023Article
- Design and characterization of PROTAC degraders specific to protein N-terminal methyltransferase 1.European journal of medicinal chemistry · 2022Article
- Venglustat Inhibits Protein N-Terminal Methyltransferase 1 in a Substrate-Competitive Manner.Journal of medicinal chemistry · 2022Article
- Article
- Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13.Life (Basel, Switzerland) · 2021Review
- Past, present, and perspectives of protein N-terminal methylation.Current opinion in chemical biology · 2021Review
- Structure-based Discovery of Cell-Potent Peptidomimetic Inhibitors for Protein N-Terminal Methyltransferase 1.ACS medicinal chemistry letters · 2021Article
- Selective Peptidomimetic Inhibitors of NTMT1/2: Rational Design, Synthesis, Characterization, and Crystallographic Studies.Journal of medicinal chemistry · 2020Article
- Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogues.Journal of medicinal chemistry · 2020Article
- Optimization of High-Throughput Methyltransferase Assays for the Discovery of Small Molecule Inhibitors.ACS combinatorial science · 2020Article
- Chemical Biology of Protein N-Terminal Methyltransferases.Chembiochem : a European journal of chemical biology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
α-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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.