Figure 6.
Selectivity of compound 4. (A) Structural alignment of MERS-PLpro with two human deubiquitinating enzymes. The aligned catalytic triads of two human ubiquitin C-terminal hydrolases, hUCH-L1 (green, PDB: 2ETL)38 and hUCH-L3 (orange, PDB: 1UCH),39 are shown with that of MERS-PLpro (tan, PDB: 4RNA) in the expanded box. (B) Selectivity of the confirmed hit compound 4. In addition to two human cysteine proteases (hUCH-L1 and hUCH-L3), two unrelated enzymes, Hepatitis C Virus NS3 serine protease (NS3) and Bacillus anthracis dihydroorotase (PyrC), were also tested along with both PLpro enzymes.