Activation and maturation of SARS-CoV main protease
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The worldwide outbreak of the severe acute respiratory syndrome (SARS) in 2003 was due to the transmission of SARS coronavirus (SARS-CoV). The main protease (Mpro) of SARS-CoV is essential for the viral life cycle, and is considered to be an attractive target of anti-SARS drug development. As a key enzyme for proteolytic processing of viral polyproteins to produce functional non-structure proteins, Mpro is first auto-cleaved out of polyproteins. The monomeric form of Mpro is enzymatically inactive, and it is activated through homo-dimerization which is strongly affected by extra residues to both ends of the mature enzyme. This review provides a summary of the related literatures on the study of the quaternary structure, activation, and self-maturation of Mpro over the past years.
Keywordssevere acute respiratory syndrome Mpro structure dimerization
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- Chen, S., Chen, L., Tan, J., Chen, J., Du, L., Sun, T., Shen, J., Chen, K., Jiang, H., and Shen, X. (2005). Severe acute respiratory syndrome coronavirus 3C-like proteinase N terminus is indispensable for proteolytic activity but not for enzyme dimerization. Biochemical and thermodynamic investigation in conjunction with molecular dynamics simulations. J Biol Chem 280, 164–173.CrossRefGoogle Scholar
- Chen, S., Hu, T., Zhang, J., Chen, J., Chen, K., Ding, J., Jiang, H., and Shen, X. (2008a). Mutation of Gly-11 on the dimer interface results in the complete crystallographic dimer dissociation of severe acute respiratory syndrome coronavirus 3C-like protease: crystal structure with molecular dynamics simulations. J Biol Chem 283, 554–564.CrossRefGoogle Scholar
- Shi, J., Wei, Z., and Song, J. (2004). Dissection study on the severe acute respiratory syndrome 3C-like protease reveals the critical role of the extra domain in dimerization of the enzyme: defining the extra domain as a new target for design of highly specific protease inhibitors. J Biol Chem 279, 24765–24773.CrossRefGoogle Scholar
- Snijder, E.J., Bredenbeek, P.J., Dobbe, J.C., Thiel, V., Ziebuhr, J., Poon, L.L., Guan, Y., Rozanov, M., Spaan, W.J., and Gorbalenya, A.E. (2003). Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol 331, 991–1004.CrossRefGoogle Scholar
- Tan, J., Verschueren, K.H., Anand, K., Shen, J., Yang, M., Xu, Y., Rao, Z., Bigalke, J., Heisen, B., Mesters, J.R., et al. (2005). pHdependent conformational flexibility of the SARS-CoV main proteinase (M(pro)) dimer: molecular dynamics simulations and multiple X-ray structure analyses. J Mol Biol 354, 25–40.CrossRefGoogle Scholar
- Wei, P., Li, C.M., Zhou, L., Liu, Y., and Lai, L.H. (2010). Substrate Binding and Homo Dimerization of SARS 3CL Proteinase are Mutual Allosteric Effectors. Acta Phys Chim Sin 26, 5.Google Scholar
- Zhong, N., Zhang, S., Xue, F., Kang, X., Zou, P., Chen, J., Liang, C., Rao, Z., Jin, C., Lou, Z., et al. (2009). C-terminal domain of SARS-CoV main protease can form a 3D domain-swapped dimer. Protein Sci 18, 839–844.Google Scholar