title: Structural and functional characterization of MERS coronavirus papain-like protease.
abstract: BACKGROUND
  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 (PLpro) 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 PLpro is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PLpro is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PLpro exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PLpro. A natural mutation, Leu105, is the major reason for this difference.
  
  
  CONCLUSIONS
  Overall, MERS-CoV PLpro 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 PLpro family, which is applicable to develop strategies inhibiting PLpro against highly pathogenic coronaviruses.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Lin
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Chuang
authors.forename: Chiao-Che
authors.initials: CC
authors.lastname: Chen
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Cheng
authors.forename: Kai-Wen
authors.initials: KW
authors.lastname: Cheng
authors.forename: Chao-Hsiung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan. fish3970@gmail.com.
authors.forename: Chiao-Yin
authors.initials: CY
authors.lastname: Sun
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Chou
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D005060:Europe; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007477:Ions / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D014764:Viral Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D007477:Ions; D008670:Metals; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases