Summary for 8Z7C
| Entry DOI | 10.2210/pdb8z7c/pdb |
| Descriptor | Histone-lysine N-methyltransferase EHMT2, ZINC ION, SINEFUNGIN, ... (5 entities in total) |
| Functional Keywords | histone lysine methyltransferase, inhibitor, protein-inhibitor complex, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 67541.25 |
| Authors | Niwa, H.,Shirai, F.,Sato, S.,Nishigaya, Y.,Ihara, K.,Shirouzu, M.,Umehara, T. (deposition date: 2024-04-20, release date: 2025-01-22) |
| Primary citation | Nishigaya, Y.,Takase, S.,Sumiya, T.,Sato, T.,Niwa, H.,Sato, S.,Nakata, A.,Matsuoka, S.,Maemoto, Y.,Hashimoto, N.,Namie, R.,Honma, T.,Umehara, T.,Shirouzu, M.,Koyama, H.,Yoshida, M.,Ito, A.,Shirai, F. Structure-based development of novel substrate-type G9a inhibitors as epigenetic modulators for sickle cell disease treatment. Bioorg.Med.Chem.Lett., 110:129856-129856, 2024 Cited by PubMed Abstract: The discovery and development of structurally distinct lysine methyltransferase G9a inhibitors have been the subject of intense research in epigenetics. Structure-based optimization was conducted, starting with the previously reported seed compound 7a and lead to the identification of a highly potent G9a inhibitor, compound 7i (IC = 0.024 μM). X-ray crystallography for the ligand-protein interaction and kinetics study, along with surface plasmon resonance (SPR) analysis, revealed that compound 7i interacts with G9a in a unique binding mode. In addition, compound 7i caused attenuation of cellular H3K9me2 levels and induction of γ-globin mRNA expression in HUDEP-2 cells in a dose-dependent manner. PubMed: 38914346DOI: 10.1016/j.bmcl.2024.129856 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.52 Å) |
Structure validation
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