Backgrounds A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL pro ) is expressed, and its structural and functional consequences are elucidated. Results Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL pro is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL pro is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL pro exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL pro . A natural mutation, Leu105, is the major reason for this difference. Conclusions Overall, MERS-CoV PL pro bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL pro family, which is applicable to develop strategies inhibiting PL pro against highly pathogenic coronaviruses.
【저자키워드】 Papain-like protease, antiviral target, Deubiquitination, MERS coronavirus, 【초록키워드】 Coronaviruses, coronavirus, therapy, SARS-CoV, virus, MERS-CoV, Saudi Arabia, antiviral drug, Jeddah, CoV, kinetic, Middle East, natural mutation, Fatality rate, proteolytic activity, respiratory syndrome coronavirus, monomer, Coronaviral, ultracentrifugation, highly pathogenic, European country, Result, develop, spread to, indicated, functional, expressed, demonstrated, analysis, inhibiting, exhibit, Circular, functional consequence, organized, proteolytic, 【제목키워드】 functional,