29GE
Crystal structure of human METTL1 in complex with OBV617 (compound B19)
This is a non-PDB format compatible entry.
Summary for 29GE
| Entry DOI | 10.2210/pdb29ge/pdb |
| Descriptor | tRNA (guanine-N(7)-)-methyltransferase, DI(HYDROXYETHYL)ETHER, GLYCEROL, ... (6 entities in total) |
| Functional Keywords | mettl1, m7g, inhibitor, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29944.07 |
| Authors | Nai, F.,Bobileva, O.,Caflisch, A. (deposition date: 2026-03-10, release date: 2026-08-26, Last modification date: 2026-09-23) |
| Primary citation | Bobileva, O.,Nai, F.,Niedrite, S.,Mayordomo Soler, L.,Leite, I.,Caflisch, A. Adenosine 5'-Carboxamide-Based Inhibitors of METTL1. Acs Med.Chem.Lett., 17:1941-1947, 2026 Cited by PubMed Abstract: METTL1 is the human RNA methyltransferase that catalyzes the methylation of 7-guanosine in RNA. Overexpression of METTL1 has been linked to cancer, and increasing evidence supports the therapeutic potential of METTL1 inhibition in oncology. In this study, we have optimized a series of adenosine 5'-carboxamide derivatives as METTL1 inhibitors through structure-guided modifications of a previously discovered hit compound. The advanced inhibitor shows an IC of 1 μM in an enzymatic assay, which is a 178-fold improvement with respect to the initial hit. The crystal structure of the des-methyl analogue of (compound , IC = 0.4 μM) provides evidence that the benzylpiperazine moiety is accommodated within the guanosine-binding subsite of METTL1. The inhibitor shows high solubility and metabolic stability and is selective against a panel of seven histone methyltransferases and the RNA-methyltransferase METTL3/METTL14. PubMed: 42741303DOI: 10.1021/acsmedchemlett.6c00203 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.89 Å) |
Structure validation
Download full validation report
