Novel starting points for fragment-based drug design against human heat-shock protein 90 identified using crystallographic fragment screening

Huang, L.; Wang, W.; Zhu, Z.; Li, Q.; Li, M.; Zhou, H.; Xu, Q.; Wen, W.; Wang, Q.; Yu, F.

doi:10.1107/S2052252524012247

Figure 5
Fragment binding to site 2 adjacent to the ATP lid results in changes to the backbone. (a) The location of 13 clustered fragments is illustrated. A pocket is formed between helices 23–36 and 111–124. (b) Detailed interactions between the fragment and HSP90^N are depicted. Fragment 2X-5009 (gray) interacts solely with water through hydrogen bonds, yet is deeply embedded within this pocket. Hydrogen bonds are represented as black dashed lines, while small red dots indicate water molecules. (c) A comparison of the opening and closing of the ATP lid is shown. The blue color represents the open conformation following fragment binding to this site, while green (PDB entry 8b7i; Henot et al., 2022

) denotes the closed conformation.