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Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants

Fig 2

Structural basis for UbV inhibition of MERS-CoV PLpro.

(A-C) Crystal structure of (A) the MERS-CoV PLpro-ME.4 complex, (B) the MERS-CoV PLpro-ME.2 complex, and (C) the MERS-CoV PLpro-Ub.wt complex (PDB ID: 4RF0). PLpro domains are shown as surface representations, and coloured in wheat, gray and chartreuse for the PLpro-ME.4, -ME.2 and–Ub.wt complexes, respectively. ME.4, ME.2 and Ub.wt are shown as tubes and coloured in marine, red and orange, respectively. (D) Close up of a superposition of the MERS-CoV PLpro-ME.4 and -ME.2 complexes (left panel) showing detailed interactions between PLpro and residue Ile70 of ME.4 or ME.2, and a comparison (right panel) of the same region in the PLpro-Ub.wt complex. PLpro residues are shown as sticks and labeled with in italics with asterisks. (E) Close up of the MERS-CoV PLpro-ME.4 and -ME.2 complexes (left panel) showing detailed interactions between PLpro and residue Phe46 of ME.4 or ME.2, and a comparison (right panel) of the same region in the PLpro-Ub.wt complex. (F) Close up of the MERS-CoV PLpro-ME.4 and -ME.2 complexes (left panel) showing detailed interactions between PLpro and residue Tyr64 of ME.4 or ME.2, and a comparison (right panel) of the same region in the PLpro-Ub.wt complex. (G) Close up of ME.4 residue Asn74 bound near the active site of PLpro. Hydrogen bonds are represented by dashed black lines. (H) Close up of the C-terminus of Ub.wt covalently bound in the active site of PLpro. (I) Close up of ME.2 residue Pro74 bound near the active site of PLpro. Figures were generated using PyMOL [61].

Fig 2

doi: https://doi.org/10.1371/journal.ppat.1006372.g002