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. 2022 Apr 11;10:832431. doi: 10.3389/fchem.2022.832431

FIGURE 4.

FIGURE 4

The bound compounds interfere with key residues for substrate binding at the S1 (yellow frame) and S2 (pink frame) site. (A) Overlay of ubiquitin bound to PLpro (PDB: 6xaa, PLpro light green, ubiquitin green) and the hydrazone bound structure (PLpro grey, H1 magenta) showing the rearrangement of several PLpro-ubiquitin interacting side chains to form hydrogen bonds with the compound. (B,C) Overlay of PLpro complexed with human ISG15 (PDB: 7rbs, PLpro light pink, ISG15 purple) and PLpro bound with hydrazone H1 and thiosemicarbazone T2 (PLpro grey, H1 magenta, T2 green) at the S1 and S2 sites respectively highlighting the structural differences in binding the compound or substrate.