ArticleJournal of molecular biology2010
Insights into cleavage specificity from the crystal structure of foot-and-mouth disease virus 3C protease complexed with a peptide substrate.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Foot-and-mouth disease virus 3C protease as virulence determinant plays multiple roles in cleaving viral polyprotein and host factors.Virulence · 2026Review
- In silico, in vitro, and in vivo evaluation of the antiviral potential of glycyrrhizic acid and chitosan nanoparticles against foot and mouth disease virus.Virology journal · 2026Article
- STING1 negatively regulates translation and replication of foot-and-mouth disease virus independently of interferon and is antagonized by the viral proteins 3C and 2B.Virologica Sinica · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Virulence determinant of Senecavirus A: 3C protein functions as a protease to cleave viral polyprotein and host factors.Virulence · 2025Review
- Elucidating the structural dynamics induced by active site mutations in 3C protease of foot-and-mouth disease virus.PloS one · 2025Article
- Production of virus-like particles of FMDV by 3C protease cleaving precursor polyprotein P1 in vitro.Applied microbiology and biotechnology · 2024Article
- The antiviral response triggered by the cGAS/STING pathway is subverted by the foot-and-mouth disease virus proteases.Cellular and molecular life sciences : CMLS · 2024Article
- Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs.Molecules (Basel, Switzerland) · 2023Article
- Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA.Viruses · 2023Review
- Small Molecules Targeting 3C Protease Inhibit FMDV Replication and Exhibit Virucidal Effect in Cell-Based Assays.Viruses · 2023Article
- Insights into Polyprotein Processing and RNA-Protein Interactions in Foot-and-Mouth Disease Virus Genome Replication.Journal of virology · 2023Article
- Allosteric regulation of Senecavirus A 3Cpro proteolytic activity by an endogenous phospholipid.PLoS pathogens · 2023Article
- Structure-based virtual screening and molecular dynamics studies to explore potential natural inhibitors against 3C protease of foot-and-mouth disease virus.Frontiers in veterinary science · 2023Article
- Preventive effects of quercetin against foot-and-mouth disease virusFrontiers in microbiology · 2023Article
- Andrographolide and Deoxyandrographolide Inhibit Protease and IFN-Antagonist Activities of Foot-and-Mouth Disease Virus 3CAnimals : an open access journal from MDPI · 2022Article
- An intermolecular salt bridge linking substrate binding and P1 substrate specificity switch of arterivirus 3C-like proteases.Computational and structural biotechnology journal · 2022Article
- Natural Phytochemicals, Luteolin and Isoginkgetin, Inhibit 3C Protease and Infection of FMDV, In Silico and In Vitro.Viruses · 2021Article
- Innate immune evasion mediated by picornaviral 3C protease: Possible lessons for coronaviral 3C-like protease?Reviews in medical virology · 2021Review
- Foot-and-Mouth Disease Virus 3C Protease Antagonizes Interferon Signaling and C142T Substitution Attenuates the FMD Virus.Frontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Picornavirus replication is critically dependent on the correct processing of a polyprotein precursor by 3C protease(s) (3C(pro)) at multiple specific sites with related but non-identical sequences. To investigate the structural basis of its cleavage specificity, we performed the first crystallographic structural analysis of non-covalent complexes of a picornavirus 3C(pro) with peptide substrates. The X-ray crystal structure of the foot-and-mouth disease virus 3C(pro), mutated to replace the catalytic Cys by Ala and bound to a peptide (APAKQ|LLNFD) corresponding to the P5-P5' region of the VP1-2A cleavage junction in the viral polyprotein, was determined up to 2.5 A resolution. Comparison with free enzyme reveals significant conformational changes in 3C(pro) on substrate binding that lead to the formation of an extended interface of contact primarily involving the P4-P2' positions of the peptide. Strikingly, the deep S1' specificity pocket needed to accommodate P1'-Leu only forms when the peptide binds. Substrate specificity was investigated using peptide cleavage assays to show the impact of amino acid substitutions within the P5-P4' region of synthetic substrates. The structure of the enzyme-peptide complex explains the marked substrate preferences for particular P4, P2 and P1 residue types, as well as the relative promiscuity at P3 and on the P' side of the scissile bond. Furthermore, crystallographic analysis of the complex with a modified VP1-2A peptide (APAKE|LLNFD) containing a Gln-to-Glu substitution reveals an identical mode of peptide binding and explains the ability of foot-and-mouth disease virus 3C(pro) to cleave sequences containing either P1-Gln or P1-Glu. Structure-based mutagenesis was used to probe interactions within the S1' specificity pocket and to provide direct evidence of the important contribution made by Asp84 of the Cys-His-Asp catalytic triad to proteolytic activity. Our results provide a new level of detail in our understanding of the structural basis of polyprotein cleavage by 3C(pro).
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