KAT6A–inhibitor co-crystal structures: tackling a challenging crystallization target via two alternative approaches

Puetter, V.; Bouché, L.; Nowak-Reppel, K.; Ferrara, S.J.; Gradl, S.N.; Korr, D.; Strathdee, C.A.; ter Laak, A.; Hillig, R.C.

doi:10.1107/S2059798326008545

Figure 8
Exploiting the hydrophobic side pocket in the benzofuran-acylsulfonamide series and in the benzothiadiazine series. (a) shows the superimposition of KAT6A^mutCys in complex with AcCoA (PDB entry 29uq; C atoms in grey) and in complex with BAY-184 (PDB entry 9fkr; ter Laak et al., 2024

; C arbon atoms in lilac). The location of a hydrophobic side pocket is indicated by an orange box. (b) shows the same superimposition as in (a), but now additionally with the co-complex of KAT8^mutant/MYST^cryst and compound 2 (PDB entry 29ut; C atoms in green); (c) shows the superimposition of KAT6A^mutCys in complex with AcCoA and the co-complex structures of KAT8^mutant/MYST^cryst with compound 2 (PDB entry 29ut; C atoms in green) and with the benzo-thiadiazine Example 41 (PDB entry 29uu; C atoms in cyan).

STRUCTURAL
BIOLOGY

ISSN: 2059-7983

Volume 82| Part 9| September 2026| Pages 1111-1124

https://doi.org/10.1107/S2059798326008545

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