3MO0
Human G9a-like (GLP, also known as EHMT1) in complex with inhibitor E11
Summary for 3MO0
| Entry DOI | 10.2210/pdb3mo0/pdb |
| Related | 3FPD 3MO2 3MO5 |
| Descriptor | Histone-lysine N-methyltransferase, H3 lysine-9 specific 5, S-ADENOSYL-L-HOMOCYSTEINE, N~4~-(1-benzylpiperidin-4-yl)-N~2~-[3-(dimethylamino)propyl]-6,7-dimethoxyquinazoline-2,4-diamine, ... (6 entities in total) |
| Functional Keywords | epigenetics, histone lysine methylation, enzymatic inhibition, lysine mimics, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: Q9H9B1 |
| Total number of polymer chains | 2 |
| Total formula weight | 68643.38 |
| Authors | Chang, Y.,Horton, J.R.,Cheng, X. (deposition date: 2010-04-22, release date: 2010-06-30, Last modification date: 2024-11-20) |
| Primary citation | Chang, Y.,Ganesh, T.,Horton, J.R.,Spannhoff, A.,Liu, J.,Sun, A.,Zhang, X.,Bedford, M.T.,Shinkai, Y.,Snyder, J.P.,Cheng, X. Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases. J.Mol.Biol., 400:1-7, 2010 Cited by PubMed Abstract: Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the histone code. One common feature of these activities is the recognition of lysines in methylated and unmethylated states, whether they are substrates, reaction products, or binding partners. We applied the concept of adding a lysine mimic to an established inhibitor (BIX-01294) of histone H3 lysine 9 methyltransferases G9a and G9a-like protein by including a 5-aminopentyloxy moiety, which is inserted into the target lysine-binding channel and becomes methylated by G9a-like protein, albeit slowly. The compound enhances its potency in vitro and reduces cell toxicity in vivo. We suggest that adding a lysine or methyl-lysine mimic should be considered in the design of small-molecule inhibitors for other methyl-lysine writers, erasers, and readers. PubMed: 20434463DOI: 10.1016/j.jmb.2010.04.048 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.78 Å) |
Structure validation
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