7EZG
The structure of the human METTL6 enzyme in complex with SAH
Summary for 7EZG
| Entry DOI | 10.2210/pdb7ezg/pdb |
| Descriptor | tRNA N(3)-methylcytidine methyltransferase METTL6, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total) |
| Functional Keywords | m3c, trna modifications, cocrystal, mettl6, toxin, methyltransferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 36170.20 |
| Authors | |
| Primary citation | Chen, R.,Zhou, J.,Liu, L.,Mao, X.L.,Zhou, X.,Xie, W. Crystal structure of human METTL6, the m 3 C methyltransferase. Commun Biol, 4:1361-1361, 2021 Cited by PubMed Abstract: In tRNA, the epigenetic mC modification at position 32 in the anticodon loop is highly conserved in eukaryotes, which maintains the folding and basepairing functions of the anticodon. However, the responsible enzymes METTL2 and METTL6 were identified only in recent years. The loss of human METTL6 (hMETTL6) affects the translational process and proteostasis in cells, while in mESCs cells, it leads to defective pluripotency potential. Despite its important functions, the catalytic mechanism of the C32 methylation by this enzyme is poorly understood. Here we present the 1.9 Å high-resolution crystal structure of hMETTL6 bound by SAH. The key residues interacting with the ligand were identified and their roles were confirmed by ITC. We generated a docking model for the hMETTL6-SAH-CMP ternary complex. Interestingly, the CMP molecule binds into a cavity in a positive patch with the base ring pointing to the inside, suggesting a flipped-base mechanism for methylation. We further generated a model for the quaternary complex with tRNA as a component, which reasonably explained the biochemical behaviors of hMETTL6. Taken together, our crystallographic and biochemical studies provide important insight into the molecular recognition mechanism by METTL6 and may aid in the METTL-based rational drug design in the future. PubMed: 34862464DOI: 10.1038/s42003-021-02890-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
