7ACD
Crystal structure of the human METTL3-METTL14 complex with compound T30 (UZH1a)
Summary for 7ACD
| Entry DOI | 10.2210/pdb7acd/pdb |
| Descriptor | N6-adenosine-methyltransferase catalytic subunit, N6-adenosine-methyltransferase non-catalytic subunit, 4-[(4,4-dimethylpiperidin-1-yl)methyl]-2-oxidanyl-~{N}-[[(3~{R})-3-oxidanyl-1-[6-[(phenylmethyl)amino]pyrimidin-4-yl]piperidin-3-yl]methyl]benzamide, ... (6 entities in total) |
| Functional Keywords | inhibitor, complex, mettl3, sinefungin, mettl14, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 62407.39 |
| Authors | Bedi, R.K.,Huang, D.,Caflisch, A. (deposition date: 2020-09-10, release date: 2020-10-28, Last modification date: 2024-11-13) |
| Primary citation | Moroz-Omori, E.V.,Huang, D.,Kumar Bedi, R.,Cheriyamkunnel, S.J.,Bochenkova, E.,Dolbois, A.,Rzeczkowski, M.D.,Li, Y.,Wiedmer, L.,Caflisch, A. METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes. Chemmedchem, 16:3035-3043, 2021 Cited by PubMed Abstract: The methylase METTL3 is the writer enzyme of the N -methyladenosine (m A) modification of RNA. Using a structure-based drug discovery approach, we identified a METTL3 inhibitor with potency in a biochemical assay of 280 nM, while its enantiomer is 100 times less active. We observed a dose-dependent reduction in the m A methylation level of mRNA in several cell lines treated with the inhibitor already after 16 h of treatment, which lasted for at least 6 days. Importantly, the prolonged incubation (up to 6 days) with the METTL3 inhibitor did not alter levels of other RNA modifications (i. e., m A, m A , m G), suggesting selectivity of the developed compound towards other RNA methyltransferases. PubMed: 34237194DOI: 10.1002/cmdc.202100291 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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