User:Ann Taylor/SARS-CoV2 MPro

The main protease is a cysteine protease that is essential for the viral life cycle. It is forms a <scene name='95/952725/Dimer/1'>homodimer</scene> consisting of the perpendicular protomers A and B. One protomer consists of <scene name='86/866577/Domains/2'>three domains</scene>. Domains I and II form an antiparallel chymotrypsin-like ß-barrel structure. Domain III (C-terminal end) consist of five alpha-helices arranged in an antiparallel cluster. <ref> Yang, H., Yang, M., Ding, Y., Liu, Y., Lou, Z., Zhou, Z., Sun, L., Mo, L., Ye, S., Pang, H., Gao, G. F., Anand, K., Bartlam, M., Hilgenfeld, R. & Rao, Z. (2003). Proc Natl Acad Sci U S A. 100, 13190–13195. </ref> <ref name=”Xu”> Xu, T., Ooi, A., Lee, H. C., Wilmouth, R., Liu, D. X. & Lescar, J. (2005). Acta Crystallogr Sect F Struct Biol Cryst Commun. 61, 964–966. </ref> The substrate binding site involves a <scene name='86/866577/Active_site/2'>catalytic dyad</scene> consisting of the residues Cys145 and His41. S1 is a <scene name='95/952725/Substrate_binding_site/1'>substrate binding pocket</scene> which lies next to the catalytic dyad and consists of the side chains Phe 140, His 163 and the backbone atoms of Glu166, Asn142, Gly 143 and His172. It confers absolute specificity for the Gln-P1 substrate residue on the enzyme as the carbonyl oxygen of Gln-P1 is stabilized by an <scene name='86/866577/Oxyanion_hole/1'>oxyanion hole</scene> which is formed by amide groups of Gly143 and the catalytic Cys145. <ref> Gorbalenya, A. E., Snijder, E. J. & Ziebuhr, J. (2000). Journal of General Virology. 81, 853–879. </ref> <ref> Xue, X., Yu, H., Yang, H., Xue, F., Wu, Z., Shen, W., Li, J., Zhou, Z., Ding, Y., Zhao, Q., Zhang, X. C., Liao, M., Bartlam, M. & Rao, Z. (2008). Journal of Virology. 82, 2515–2527. </ref> Hence, polyproteins are cleaved within the Leu-Gln↓(Ser, Ala, Gly) sequence. <ref> Rut, W., Groborz, K., Zhang, L., Sun, X., Zmudzinski, M., Hilgenfeld, R. & Drag, M. (2020). BioRxiv. 2020.03.07.981928. </ref>

The main protease is a cysteine protease that is essential for the viral life cycle. It is forms a <scene name='95/952725/Dimer/1'>homodimer</scene> consisting of the perpendicular protomers A and B. One protomer consists of <scene name='86/866577/Domains/2'>three domains</scene>. Domains I and II form an antiparallel chymotrypsin-like ß-barrel structure. Domain III (C-terminal end) consist of five alpha-helices arranged in an antiparallel cluster. <ref> Yang, H., Yang, M., Ding, Y., Liu, Y., Lou, Z., Zhou, Z., Sun, L., Mo, L., Ye, S., Pang, H., Gao, G. F., Anand, K., Bartlam, M., Hilgenfeld, R. & Rao, Z. (2003). Proc Natl Acad Sci U S A. 100, 13190–13195. </ref> <ref name=”Xu”> Xu, T., Ooi, A., Lee, H. C., Wilmouth, R., Liu, D. X. & Lescar, J. (2005). Acta Crystallogr Sect F Struct Biol Cryst Commun. 61, 964–966. </ref> The substrate binding site involves a <scene name='86/866577/Active_site/2'>catalytic dyad</scene> consisting of the residues Cys145 and His41. S1 is a <scene name='95/952725/Substrate_binding_site/1'>substrate binding pocket</scene> which lies next to the catalytic dyad and consists of the side chains Phe 140, His 163 and the backbone atoms of Glu166, Asn142, Gly 143 and His172. It confers absolute specificity for the Gln-P1 substrate residue on the enzyme as the carbonyl oxygen of Gln-P1 is stabilized by an <scene name='86/866577/Oxyanion_hole/1'>oxyanion hole</scene> which is formed by amide groups of Gly143 and the catalytic Cys145. <ref> Gorbalenya, A. E., Snijder, E. J. & Ziebuhr, J. (2000). Journal of General Virology. 81, 853–879. </ref> <ref> Xue, X., Yu, H., Yang, H., Xue, F., Wu, Z., Shen, W., Li, J., Zhou, Z., Ding, Y., Zhao, Q., Zhang, X. C., Liao, M., Bartlam, M. & Rao, Z. (2008). Journal of Virology. 82, 2515–2527. </ref> Hence, polyproteins are cleaved within the Leu-Gln↓(Ser, Ala, Gly) sequence. <ref> Rut, W., Groborz, K., Zhang, L., Sun, X., Zmudzinski, M., Hilgenfeld, R. & Drag, M. (2020). BioRxiv. 2020.03.07.981928. </ref>