User:Dora Bonadio/Sandbox 1 - Revision history

Dora Bonadio at 17:33, 21 June 2020

Dora Bonadio — Sun, 21 Jun 2020 17:33:38 GMT

←Older revision		Revision as of 17:33, 21 June 2020
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	== An attractive drug target ==		== An attractive drug target ==
-	As have been shown, because of its importance for viral replication, inhibiting SARS-CoV-2 M<sup>pro</sup> activity could lead to viral replication blockage <ref name="Crystal_structure" /><ref name="ofmpro" />. Moreover, no human proteases has been reported to have a similar cleavage specificity and so, in this aspect, M<sup>pro</sup> inhibitors toxic side-effects may be reduced <ref name="sars_mers" />. Therefore, CoV M<sup>pro</sup> has been an attractive drug target among coronaviruses <ref name="sars_mers" /> and so it is for COVID-19 <ref name="Crystal_structure" /><ref name="ofmpro" />. Indeed, virtual drug screening, structure-assisted drug design, and high-throughput screening are been used to repurpose approved pharmaceutical drug and drug candidates targeting SARS-CoV-2 M<sup>pro</sup> <ref name="ofmpro" /><ref name="elucidation"> Mirza, Muhammad Usman, and Matheus Froeyen. 2020. ‘Structural Elucidation of SARS-CoV-2 Vital Proteins: Computational Methods Reveal Potential Drug Candidates against Main Protease, Nsp12 Polymerase and Nsp13 Helicase’. Journal of Pharmaceutical Analysis, April. Doi:[https://doi.org/10.1016/j.jpha.2020.04.008].</ref>. Furthermore, a study carrying the pharmacokinetic characterization of an optimized M<sup>pro</sup> <scene name='84/845941/13b/1'>α-ketoamide inhibitor</scene> ~~provides~~ useful framework for development of this kind of inhibitors toward coronaviruses <ref name="Crystal_structure" />. It was showed that the α-ketoamide inhibitor interacts with the catalytic ~~site of the enzyme~~ through ~~two~~ hydrogen ~~bonding interactions~~, as can be seen in the complex formed between SARS-CoV-2 M<sup>pro</sup> and ~~an <scene name='84/845941/13b2/1'>~~α-ketoamide inhibitor~~</scene>~~ <ref name="Crystal_structure" />.	+	As have been shown, because of its importance for viral replication, inhibiting SARS-CoV-2 M<sup>pro</sup> activity could lead to viral replication blockage <ref name="Crystal_structure" /><ref name="ofmpro" />. Moreover, no human proteases has been reported to have a similar cleavage specificity and so, in this aspect, M<sup>pro</sup> inhibitors toxic side-effects may be reduced <ref name="sars_mers" />. Therefore, CoV M<sup>pro</sup> has been an attractive drug target among coronaviruses <ref name="sars_mers" /> and so it is for COVID-19 <ref name="Crystal_structure" /><ref name="ofmpro" />. Indeed, virtual drug screening, structure-assisted drug design, and high-throughput screening are been used to repurpose approved pharmaceutical drug and drug candidates targeting SARS-CoV-2 M<sup>pro</sup> <ref name="ofmpro" /><ref name="elucidation"> Mirza, Muhammad Usman, and Matheus Froeyen. 2020. ‘Structural Elucidation of SARS-CoV-2 Vital Proteins: Computational Methods Reveal Potential Drug Candidates against Main Protease, Nsp12 Polymerase and Nsp13 Helicase’. Journal of Pharmaceutical Analysis, April. Doi:[https://doi.org/10.1016/j.jpha.2020.04.008].</ref>. Furthermore, a study carrying the pharmacokinetic characterization of an optimized M<sup>pro</sup> <scene name='84/845941/13b/1'>α-ketoamide inhibitor</scene> provided useful framework for development of this kind of inhibitors toward coronaviruses <ref name="Crystal_structure" />. It was showed that the <scene name='84/845941/13b2/1'>α-ketoamide inhibitor</scene> interacts with the catalytic residue His41 and with residues Gly143 and Ser144 through hydrogen bonds, and that there is a nucleophilic attack of the catalytic Cys145 onto the α-keto group of the inhibitor. This can be seen in the <scene name='84/845941/Inhibitor_and_bindingsite_bond/1'>complex</scene> formed between SARS-CoV-2 M<sup>pro</sup> and the α-ketoamide inhibitor <ref name="Crystal_structure" />.

	== External Resources ==		== External Resources ==

Dora Bonadio at 00:13, 21 June 2020

Dora Bonadio — Sun, 21 Jun 2020 00:13:23 GMT

←Older revision		Revision as of 00:13, 21 June 2020
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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> ==

Dora Bonadio at 19:34, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 19:34:19 GMT

←Older revision		Revision as of 19:34, 20 June 2020
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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 substrate-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" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==

Dora Bonadio at 19:23, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 19:23:20 GMT

←Older revision		Revision as of 19:23, 20 June 2020
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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 Cys145 and His41 <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 substrate-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 substrate-binding site.<ref name="Crystal_structure" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==

Dora Bonadio at 19:01, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 19:01:37 GMT

←Older revision		Revision as of 19:01, 20 June 2020
Line 10:		Line 10:

	== 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 Cys145 and His41 <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 Ser1 of each monomer interacts with Glu166 of the other monomer, helping shape the substrate-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 Cys145 and His41 <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 substrate-binding site.<ref name="Crystal_structure" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==

Dora Bonadio at 18:42, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 18:42:18 GMT

←Older revision		Revision as of 18:42, 20 June 2020
Line 10:		Line 10:

	== 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 Cys145 and His41 <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 contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal ~~residues~~ of each monomer ~~interact~~ with Glu166 of the other monomer, helping shape the substrate-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 Cys145 and His41 <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 Ser1 of each monomer interacts with Glu166 of the other monomer, helping shape the substrate-binding site.<ref name="Crystal_structure" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==

Dora Bonadio at 18:22, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 18:22:45 GMT

←Older revision		Revision as of 18:22, 20 June 2020
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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 Cys145 and His41 <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 salt-bridge between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-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 Cys145 and His41 <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 contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-binding site.<ref name="Crystal_structure" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==

Dora Bonadio at 17:57, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 17:57:11 GMT

←Older revision		Revision as of 17:57, 20 June 2020
Line 10:		Line 10:

	== 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 Cys145 and His41 <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 substrate-binding site <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>. This dimerization regulation is mainly through a salt-bridge between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-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 Cys145 and His41 <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 salt-bridge between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-binding site.<ref name="Crystal_structure" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==

Dora Bonadio at 16:51, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 16:51:58 GMT

←Older revision		Revision as of 16:51, 20 June 2020
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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 five α-helices <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 Cys145 and His41 <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 substrate-binding site <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>. This dimerization regulation is mainly through a salt-bridge between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-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 Cys145 and His41 <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 substrate-binding site <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>. This dimerization regulation is mainly through a salt-bridge between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-binding site.<ref name="Crystal_structure" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==

Dora Bonadio at 16:46, 20 June 2020

Dora Bonadio — Sat, 20 Jun 2020 16:46:18 GMT

←Older revision		Revision as of 16:46, 20 June 2020
Line 10:		Line 10:

	== 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 β-barrels and domain III comprises five α-helices <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 Cys145 and His41 <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 substrate-binding site <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>. This dimerization regulation is mainly through a salt-bridge between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-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 five α-helices <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 Cys145 and His41 <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 substrate-binding site <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>. This dimerization regulation is mainly through a salt-bridge between Glu290 of one monomer and Arg4 of the other monomer.<ref name="Crystal_structure" /> Moreover, the dimer has a contact interface that is predominantly between domain II of one monomer and the N-terminal residues of other monomer. Indeed, the N-terminal residues of each monomer interact with Glu166 of the other monomer, helping shape the substrate-binding site.<ref name="Crystal_structure" />

	== Structural comparison with SARS-CoV M<sup>pro</sup> ==		== Structural comparison with SARS-CoV M<sup>pro</sup> ==