ArticleProtein & cell2010
Three-dimensional domain swapping as a mechanism to lock the active conformation in a super-active octamer of SARS-CoV main protease.
Article in Protein & cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Inhibitor-induced dimerization mediates lufotrelvir resistance in mutants of SARS-CoV-2 3C-like protease.Protein science : a publication of the Protein Society · 2025Article
- The zymogenic form of SARS-CoV-2 main protease: A discrete target for drug discovery.The Journal of biological chemistry · 2025Article
- Domain swapping: a mathematical model for quantitative assessment of structural effects.FEBS open bio · 2024Article
- A naturally occurring G11S mutation in the 3C-like protease from the SARS-CoV-2 virus dramatically weakens the dimer interface.Protein science : a publication of the Protein Society · 2024Article
- Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies.Saudi journal of biological sciences · 2023Article
- X-ray crystallographic characterization of the SARS-CoV-2 main protease polyprotein cleavage sites essential for viral processing and maturation.Nature communications · 2022Article
- Development of a colorimetric assay for the detection of SARS-CoV-2 3CLpro activity.The Biochemical journal · 2022Article
- An extended conformation of SARS-CoV-2 main protease reveals allosteric targets.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Is amyloid fibrillation related to 3D domain swapping for the C-terminal domain of SARS-CoV main protease?International journal of biological macromolecules · 2022Article
- Precursors of Viral Proteases as Distinct Drug Targets.Viruses · 2021Review
- Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds.Pharmaceuticals (Basel, Switzerland) · 2021Article
- What coronavirus 3C-like protease tells us: From structure, substrate selectivity, to inhibitor design.Medicinal research reviews · 2021Review
- The missing link: covalent linkages in structural models.Acta crystallographica. Section D, Structural biology · 2021Article
- Potential 3-chymotrypsin-like cysteine protease cleavage sites in the coronavirus polyproteins pp1a and pp1ab and their possible relevance to COVID-19 vaccine and drug development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Review
- Protein structural heterogeneity: A hypothesis for the basis of proteolytic recognition by the main protease of SARS-CoV and SARS-CoV-2.Biochimie · 2021Article
- A pocket guide on how to structure SARS-CoV-2 drugs and therapies.Biochemical Society transactions · 2020Review
- Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening.International journal of biological macromolecules · 2020Article
- Progress in Developing Inhibitors of SARS-CoV-2 3C-Like Protease.Microorganisms · 2020Review
- Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors.International journal of antimicrobial agents · 2020Article
- Discovery of Potential Flavonoid Inhibitors Against COVID-19 3CL Proteinase Based on Virtual Screening Strategy.Frontiers in molecular biosciences · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses. The main protease (M(pro)) of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the polyprotein processing. M(pro) is initially produced as part of viral polyproteins and it is matured by autocleavage. Here, we report that, with the addition of an N-terminal extension peptide, M(pro) can form a domain-swapped dimer. After complete removal of the extension peptide from the dimer, the mature M(pro) self-assembles into a novel super-active octamer (AO-M(pro)). The crystal structure of AO-M(pro) adopts a novel fold with four domain-swapped dimers packing into four active units with nearly identical conformation to that of the previously reported M(pro) active dimer, and 3D domain swapping serves as a mechanism to lock the active conformation due to entanglement of polypeptide chains. Compared with the previously well characterized form of M(pro), in equilibrium between inactive monomer and active dimer, the stable AO-M(pro) exhibits much higher proteolytic activity at low concentration. As all eight active sites are bound with inhibitors, the polyvalent nature of the interaction between AO-M(pro) and its polyprotein substrates with multiple cleavage sites, would make AO-M(pro) functionally much more superior than the M(pro) active dimer for polyprotein processing. Thus, during the initial period of SARS-CoV infection, this novel active form AOM(pro) should play a major role in cleaving polyproteins as the protein level is extremely low. The discovery of AOM(pro) provides new insights about the functional mechanism of M(pro) and its maturation process.
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