9PKU
Crystal Structure of YEATS domain of human YEATS2 in complex with LS-131 peptide
This is a non-PDB format compatible entry.
Summary for 9PKU
| Entry DOI | 10.2210/pdb9pku/pdb |
| Descriptor | YEATS domain-containing protein 2, LS-131 peptide, GLYCEROL, ... (6 entities in total) |
| Functional Keywords | atac complex, yeats2, chemical probe, gene regulation |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 34297.42 |
| Authors | |
| Primary citation | Liu, S.,Liu, J.,Wu, Y.,Yao, X.,Li, X.,Dong, X.,Li, Q.,Cheung, H.J.H.,Wong, K.Y.,Li, Y.,He, M.,Chiang, C.L.,Wong, J.W.H.,Li, H.,Wang, W.,Li, X.,Li, X.D. Complex-specific inhibitors for interrogating ATAC histone acetyltransferase complex. Nat.Chem.Biol., 22:471-481, 2026 Cited by PubMed Abstract: Histone acetyltransferases (HATs) modify chromatin to regulate gene expression. Instead of acting alone, HATs function in complexes with other proteins, leading to variations in substrate specificity, genomic localization and cellular function. To understand the complex-dependent roles of HATs, we present a chemical approach to specifically dissociate ATAC (Ada-two-A-containing) HAT complex from chromatin without perturbing other complexes. Rather than targeting the shared HAT enzyme, we developed chemical inhibitors for an ATAC-specific subunit, YEATS2. The most effective inhibitor, LS-170, specifically reduced the chromatin occupancy of the ATAC complex, decreased the ATAC-dependent histone acetylation level and downregulated the expression of ATAC-governed genes, leading to significantly suppressed tumor growth in a lung cancer mouse model. This study not only sheds light on the regulatory roles of the ATAC HAT complex in gene transcription but also provides evidence that the chemical inhibition of the ATAC complex can be a promising therapeutic strategy. PubMed: 41513852DOI: 10.1038/s41589-025-02132-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.88 Å) |
Structure validation
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