9OOF
Crystal structure of MYST acetyltransferase domain in complex with inhibitor 10e
This is a non-PDB format compatible entry.
Summary for 9OOF
| Entry DOI | 10.2210/pdb9oof/pdb |
| Descriptor | Histone acetyltransferase KAT8, ZINC ION, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | acetyltransferase, inhibitor, complex, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 35206.15 |
| Authors | Hermans, S.J.,Suwandi, A.,Parker, M.W.,Baell, J.B. (deposition date: 2025-05-15, release date: 2026-02-11) |
| Primary citation | Suwandi, A.,Jin, J.,Zhao, Y.,Mudududdla, R.,Gee, Y.S.,Deora, G.S.,Sun, Y.,Wei, H.,Huang, F.,He, J.S.,George, A.J.,Hermans, S.J.,Leaver, D.J.,Parker, M.W.,Baell, J.B. Biological Activity and Structural Biology of Current KAT6A Inhibitor Chemotypes. J.Med.Chem., 2026 Cited by PubMed Abstract: All lysine acetyltransferases (KATs) modulate biological outcomes through the acetylation of lysine side-chain amino groups facilitated by acetyl coenzyme A (AcCoA). KAT6A belongs to the class of MYST domain histone acetyltransferases (HATs), which had been regarded as undruggable. The first on-target KAT6A inhibitors with activity were reported in 2018, catalyzing intense industry interest in this enzyme as an oncology target. In this study, we experimentally evaluated representative KAT6A inhibitor chemotypes through resynthesis and comparative biochemical assays, cellular assays, and structural biology. We outline the recent history of each KAT6A inhibitor chemotype discovery, including SAR for potency, selectivity, and cellular activity. We extensively benchmark key compounds from each chemotype, augmented by new acylsulfonohydrazide analogues and a novel fused [1,2,4]thiadiazine KAT6A inhibitor subclass, which we report here for the first time, along with co-crystal structures. Additionally, we report on the activity, pharmacokinetics, and toxicology profiles of these inhibitors. PubMed: 41611522DOI: 10.1021/acs.jmedchem.5c01426 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.681 Å) |
Structure validation
Download full validation report
