6KMR

Crystal structure of human N6amt1-Trm112 in complex with SAM (space group P6122)

Summary for 6KMR

• Entry DOI: 10.2210/pdb6kmr/pdb
• Descriptor: Multifunctional methyltransferase subunit TRM112-like protein, Methyltransferase N6AMT1, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: methyltransferase, complex, protein translation, polypeptide release factor erf1, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 39404.13

Authors

Li, W.J.,Shi, Y.,Zhang, T.L.,Ye, J.,Ding, J.P. (deposition date: 2019-08-01, release date: 2019-09-18, Last modification date: 2023-11-22)

Primary citation

Li, W.,Shi, Y.,Zhang, T.,Ye, J.,Ding, J.
Structural insight into human N6amt1-Trm112 complex functioning as a protein methyltransferase.
Cell Discov, 5:51-51, 2019

PubMed Abstract: DNA methylation is an important epigenetic modification in many organisms and can occur on cytosine or adenine. N-methyladenine (6mA) exists widespreadly in bacterial genomes, which plays a vital role in the bacterial restriction-modification system. Recently, 6mA has also been reported to exist in the genomes of a variety of eukaryotes from unicellular organisms to metazoans. There were controversial reports on whether human N6amt1, which was originally reported as a glutamine MTase for eRF1, is a putative 6mA DNA MTase. We report here the crystal structure of human N6amt1-Trm112 in complex with cofactor SAM. Structural analysis shows that Trm112 binds to a hydrophobic surface of N6amt1 to stabilize its structure but does not directly contribute to substrate binding and catalysis. The active site and potential substrate-binding site of N6amt1 are dominantly negatively charged and thus are unsuitable for DNA binding. The biochemical data confirm that the complex cannot bind DNA and has no MTase activity for DNA, but exhibits activity for the methylation of Gln185 of eRF1. Our structural and biochemical data together demonstrate that N6amt1 is a bona fide protein MTase rather than a DNA MTase.

PubMed: 31636962
DOI: 10.1038/s41421-019-0121-y

Experimental method

X-RAY DIFFRACTION (2 Å)