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Figure 1
Cryo-EM structures of PDE6 and VCP/p97 in the com­plex with CB-5083. (a) The overall structure of PDE6 bound to CB-5083. The PDE6 α, β, and γ subunits are colored light blue, sky blue, and magenta, respectively. CB-5083 is shown in yellow spheres. The inset displays the experimental cryo-EM density for CB-5083 in the map. (b) Close-up view of the CB-5083 binding pocket in PDE6. Key inter­acting residues are shown in stick representation, with hy­dro­gen bonds indicated by the dashed orange lines. The transparent red oval indicates a key region of the binding pocket where there are close packing inter­actions between CB-5083 and residues in the PDE6 active site. (c) The overall structure of VCP/p97 bound to CB-5083 as we reported previously (PDB ID: 7rli). A single VCP/p97 protomer within the dodeca­mer is highlighted in sky blue. The inset displays the experimental cryo-EM density for CB-5083 in the map. (d) Close-up view of the CB-5083 binding pocket in VCP/p97. Key inter­acting residues are highlighted and labeled, with hy­dro­gen bonds indicated by dashed orange lines. In contrast to the close inter­actions seen in the PDE6 binding pocket at the site corresponding to the green oval, there is a cavity observed near the same atoms of CB-5083 in the com­plex with VCP/p97, providing an opportunity to introduce bulkier moieties in this region that would be accommodated in the VCP/p97 pocket but not in that of PDE6.

IUCrJ
Volume 13| Part 4| July 2026|
ISSN: 2052-2525
https://doi.org/10.1107/S2052252526004604