Background A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1 st October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M pro ) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. Methods and Results The crystal structure of MERS-CoV M pro indicates that it shares a similar scaffold to that of other coronaviral M pro and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M pro undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M pro is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. Conclusions MERS-CoV M pro shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M pro family.
【초록키워드】 coronavirus, Mutation, peptide, protease, virus, MERS-CoV, Saudi Arabia, Protein, Jeddah, CoV, correlation, Critical, Mutagenesis, Analysis, Middle East, Asian, enzyme, residue, domain, M pro, Fatality rate, wild-type, proteolytic activity, respiratory syndrome coronavirus, monomer, Coronaviral, ultracentrifugation, catalytic activity, highly pathogenic, European, country, FIVE, domain III, Result, spread to, investigated, required, provide, indicate, demonstrated, 【제목키워드】 MERS, assessment, catalysis,