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Basic Characteristics of Mutations
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Mutation Site
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H41A |
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Mutation Site Sentence
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Further, we solve the structures of the SARS-CoV-2 Mpro mutant (H41A) in complex with six native cleavage substrates from replicase polyproteins, and demonstrate that SARS-CoV-2 Mpro can recognize sequences as long as 10 residues but only have special selectivity for four subsites. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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Mpro |
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Standardized Encoding Gene
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ORF1a
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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35380892
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Title
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Structural basis for replicase polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2
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Author
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Zhao Y,Zhu Y,Liu X,Jin Z,Duan Y,Zhang Q,Wu C,Feng L,Du X,Zhao J,Shao M,Zhang B,Yang X,Wu L,Ji X,Guddat LW,Yang K,Rao Z,Yang H
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Journal
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Proceedings of the National Academy of Sciences of the United States of America
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Journal Info
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2022 Apr 19;119(16):e2117142119
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Abstract
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The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key enzyme, which extensively digests CoV replicase polyproteins essential for viral replication and transcription, making it an attractive target for antiviral drug development. However, the molecular mechanism of how Mpro of SARS-CoV-2 digests replicase polyproteins, releasing the nonstructural proteins (nsps), and its substrate specificity remain largely unknown. Here, we determine the high-resolution structures of SARS-CoV-2 Mpro in its resting state, precleavage state, and postcleavage state, constituting a full cycle of substrate cleavage. The structures show the delicate conformational changes that occur during polyprotein processing. Further, we solve the structures of the SARS-CoV-2 Mpro mutant (H41A) in complex with six native cleavage substrates from replicase polyproteins, and demonstrate that SARS-CoV-2 Mpro can recognize sequences as long as 10 residues but only have special selectivity for four subsites. These structural data provide a basis to develop potent new inhibitors against SARS-CoV-2.
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Sequence Data
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-
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