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Structural and functional characterization of MERS coronavirus papain-like protease.
J Biomed Sci. 2014 Jun 04; 21:54.JB

Abstract

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 (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+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableDepartment of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan. fish3970@gmail.com.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24898546

Citation

Lin, Min-Han, et al. "Structural and Functional Characterization of MERS Coronavirus Papain-like Protease." Journal of Biomedical Science, vol. 21, 2014, p. 54.
Lin MH, Chuang SJ, Chen CC, et al. Structural and functional characterization of MERS coronavirus papain-like protease. J Biomed Sci. 2014;21:54.
Lin, M. H., Chuang, S. J., Chen, C. C., Cheng, S. C., Cheng, K. W., Lin, C. H., Sun, C. Y., & Chou, C. Y. (2014). Structural and functional characterization of MERS coronavirus papain-like protease. Journal of Biomedical Science, 21, 54. https://doi.org/10.1186/1423-0127-21-54
Lin MH, et al. Structural and Functional Characterization of MERS Coronavirus Papain-like Protease. J Biomed Sci. 2014 Jun 4;21:54. PubMed PMID: 24898546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural and functional characterization of MERS coronavirus papain-like protease. AU - Lin,Min-Han, AU - Chuang,Shang-Ju, AU - Chen,Chiao-Che, AU - Cheng,Shu-Chun, AU - Cheng,Kai-Wen, AU - Lin,Chao-Hsiung, AU - Sun,Chiao-Yin, AU - Chou,Chi-Yuan, Y1 - 2014/06/04/ PY - 2014/04/23/received PY - 2014/05/19/accepted PY - 2014/6/6/entrez PY - 2014/6/6/pubmed PY - 2014/9/10/medline SP - 54 EP - 54 JF - Journal of biomedical science JO - J. Biomed. Sci. VL - 21 N2 - 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 (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. SN - 1423-0127 UR - https://www.unboundmedicine.com/medline/citation/24898546/Structural_and_functional_characterization_of_MERS_coronavirus_papain_like_protease_ L2 - https://jbiomedsci.biomedcentral.com/articles/10.1186/1423-0127-21-54 DB - PRIME DP - Unbound Medicine ER -