Fig. 1.

Structure of the MERS-CoV papain-like protease (PL^pro). (A) Cartoon view of the enzyme’s overall structure. α-Helices (cyan) and β-strands (purple) are numbered, polypeptide segments devoid of repetitive secondary structure, including loops and turns, are brown. The ubiquitin-like (Ubl) domain is encircled by a red dashed line. The catalytic domain consists of the thumb, fingers, and palm subdomains. The structural zinc ion in the fingers domain is indicated by a gray sphere. The Cα atoms of the catalytic-site cysteine (111), histidine (278), and aspartate (293) residues are also shown (yellow, blue, and red sphere, respectively). The red arrow indicates the substrate-binding region and points to the catalytic site. (B) The four cysteine ligands (Cys191, Cys194, C226 and C228) and the structural zinc ion (gray sphere) in the zinc ribbon of the fingers domain. An F_o-F_c omit density (green; contoured at 5 σ above the mean) for the zinc is shown. Sulfur atoms are shown in yellow, oxygen in red, nitrogen in blue, and carbon in light blue. The coordinative bonds between the sulfur atoms and the zinc ion are indicated by dashed red lines. (C) The catalytic triad: Cys111, His278, and Asp293. Atom colors: carbon, yellow; oxygen, red; nitrogen, blue. A 2F_o-F_c electron density (gray; contoured at 1.0 σ above the mean) is also displayed. CME111: Cys111 covalently modified by β-mercaptoethanol.