Fig. 2: Cryo-EM structure of p97 with NSC799462 triazole inhibitor.

Surface representation of the two p97 monomers. Green, orange, orange-red, and purple are the N-terminal (NTD), D1, D2, and linker domains in chain A. White (chain B) is one of the adjacent p97 monomers, which interfaces with the binding site of NSC799462. a The NSC799462 terminal methylpiperidine group approaches the adjacent D2 nucleotide-binding site at a distance of approximately 8 Å. Hot pink is the D2 domain of the adjacent p97 monomer (D2’). Light blue surfaces are cryo-EM densities for NSC799462 and ADP. b NSC799462 binding site. NSC799462 is shown in ball-and-stick. Gray, red, blue, yellow, and light green represent carbon, oxygen, nitrogen, sulfur, and fluorine atoms, respectively. Side chains of the interacting protein residues are shown in sticks. Cryo-EM density is shown in light blue surfaces. c Superposition of p97^WT | _NSC799462 and p97^WT (PDB code: 5FTK) (RMSD 1.098 Å). p97^WT structure is shown in semi-transparent white. The region following the C-terminus of the α2 G helix that adopts a different conformation in the presence of inhibitor is shown in the inset. d Superposition of p97^WT (light purple, without inhibitor) (PDB code: 5FTK) and p97^WT | _NSC799462 (orange red, with NSC799462 in surface representation) illustrates the expansion of the binding site to fit the inhibitor. All distances are measured in Å.