6DUB

Crystal structure of a methyltransferase

Summary for 6DUB

• Entry DOI: 10.2210/pdb6dub/pdb
• Descriptor: Alpha N-terminal protein methyltransferase 1B, RCC1, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total)
• Functional Keywords: methyltransferase, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 52430.17

Authors

Dong, C.,Tempel, W.,Li, Y.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2018-06-20, release date: 2018-07-25, Last modification date: 2023-10-11)

Primary citation

Dong, C.,Dong, G.,Li, L.,Zhu, L.,Tempel, W.,Liu, Y.,Huang, R.,Min, J.
An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2.
Commun Biol, 1:183-183, 2018

PubMed 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.

PubMed: 30417120
DOI: 10.1038/s42003-018-0196-2

Experimental method

X-RAY DIFFRACTION (1.2 Å)