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== Structure == | == Structure == | ||
| - | The M<sup>pro</sup> is a protein of approximately 30 kDa <ref name="replication" /><ref name="ofmpro">Jin, Zhenming, Xiaoyu Du, Yechun Xu, Yongqiang Deng, Meiqin Liu, Yao Zhao, Bing Zhang, et al. 2020. ‘Structure of M pro from SARS-CoV-2 and Discovery of Its Inhibitors’. Nature, April, 1–5. https://doi.org/10.1038/s41586-020-2223-y. </ref> consisting of two <scene name='84/845941/Monomer/3'>monomers</scene> containing 306 amino acid residues each <ref name="Crystal_structure" />. This monomers dimerize forming a <scene name='84/845941/Assembly/5'>homodimer</scene> <ref name="Crystal_structure" />. Each chain consists of <scene name='84/845941/Domains/1'>three domains</scene>: I (<scene name='84/845941/Domaini/1'>chymotrypsin-like</scene>; residues 10-99), II (<scene name='84/845941/Domains2/1'>picornavirus 3C protease-like</scene>; residues 100-182), and III (<scene name='84/845941/Domains3/1'>a globular cluster</scene>; residues 198-303). Domains I and II comprise six-stranded antiparallel <scene name='84/845941/B_barrels/1'>β-barrels</scene> and domain III comprises <scene name='84/845941/A_helices/1'>five α-helices</scene> <ref name="Crystal_structure" /><ref name="ofmpro" />. The substrate-binding site is located between domains I and II with the <scene name='84/845941/Catalyticsite/1'>catalytic site</scene> containing the amino acid residues <scene name='84/845941/Cys145_his41/1'>Cys145 and His41</scene> <ref name="Crystal_structure" />. Domain III, in turn, has been shown to be involved in the regulation of M<sup>pro</sup> dimerization, what is necessary for the catalytic activity of this enzyme once it helps to shape the <scene name='84/845941/Substrate_binding_cleft/1'>substrate-binding site</scene> <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>. This dimerization regulation is mainly through a <scene name='84/845941/Glu290_arg4/2'>salt-bridge interaction</scene> between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a <scene name='84/845941/N_terminal_interaction/1'>contact interface</scene> that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residue <scene name='84/845941/Glu166_ser1/1'>Ser1</scene> of each monomer interacts with Glu166 of the other monomer, helping shape the <scene name='84/845941/Substrate_binding_cleft/1'>substrate-binding site</scene> (notice how Glu166 is a key residue to shape the binding site).<ref name="Crystal_structure" /> | + | The M<sup>pro</sup> is a protein of approximately 30 kDa <ref name="replication" /><ref name="ofmpro">Jin, Zhenming, Xiaoyu Du, Yechun Xu, Yongqiang Deng, Meiqin Liu, Yao Zhao, Bing Zhang, et al. 2020. ‘Structure of M pro from SARS-CoV-2 and Discovery of Its Inhibitors’. Nature, April, 1–5. https://doi.org/10.1038/s41586-020-2223-y. </ref> consisting of two <scene name='84/845941/Monomer/3'>monomers</scene> containing 306 amino acid residues each <ref name="Crystal_structure" />. This monomers dimerize forming a <scene name='84/845941/Assembly/5'>homodimer</scene> <ref name="Crystal_structure" />. Each chain consists of <scene name='84/845941/Domains/1'>three domains</scene>: I (<scene name='84/845941/Domaini/1'>chymotrypsin-like</scene>; residues 10-99), II (<scene name='84/845941/Domains2/1'>picornavirus 3C protease-like</scene>; residues 100-182), and III (<scene name='84/845941/Domains3/1'>a globular cluster</scene>; residues 198-303). Domains I and II comprise six-stranded antiparallel <scene name='84/845941/B_barrels/1'>β-barrels</scene> and domain III comprises <scene name='84/845941/A_helices/1'>five α-helices</scene> <ref name="Crystal_structure" /><ref name="ofmpro" />. The substrate-binding site is located between domains I and II with the <scene name='84/845941/Catalyticsite/1'>catalytic site</scene> containing the amino acid residues <scene name='84/845941/Cys145_his41/1'>Cys145 and His41</scene> <ref name="Crystal_structure" />. Domain III, in turn, has been shown to be involved in the regulation of M<sup>pro</sup> dimerization, what is necessary for the catalytic activity of this enzyme once it helps to shape the <scene name='84/845941/Substrate_binding_cleft/1'>substrate-binding site</scene> <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>. This dimerization regulation is mainly through a <scene name='84/845941/Glu290_arg4/2'>salt-bridge interaction</scene> between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" />. Moreover, the dimer has a <scene name='84/845941/N_terminal_interaction/1'>contact interface</scene> that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residue <scene name='84/845941/Glu166_ser1/1'>Ser1</scene> of each monomer interacts with Glu166 of the other monomer, helping shape the <scene name='84/845941/Substrate_binding_cleft/1'>substrate-binding site</scene> (notice how Glu166 is a key residue to shape the binding site).<ref name="Crystal_structure" /> Therefore, The N-terminal of one monomer interacts with the other monomer by the <scene name='84/845941/Dimerization/1'>Glu166-Ser1 and Glu290-Arg1 interactions</scene> to help dimerization. |
== Structural comparison with SARS-CoV M<sup>pro</sup> == | == Structural comparison with SARS-CoV M<sup>pro</sup> == | ||
Revision as of 00:13, 21 June 2020
SARS-CoV-2 main protease (Mpro)
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