{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:47:04Z","timestamp":1791103624955,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The 2A proteinases (2A\n            <jats:sup>pro<\/jats:sup>\n            ) from the picornavirus family are multifunctional cysteine proteinases that perform essential roles during viral replication, involving viral polyprotein self-processing and shutting down host cell protein synthesis through cleavage of the eukaryotic initiation factor 4G (eIF4G) proteins. Coxsackievirus B4 (CVB4) 2A\n            <jats:sup>pro<\/jats:sup>\n            also cleaves heart muscle dystrophin, leading to cytoskeletal dysfunction and the symptoms of human acquired dilated cardiomyopathy. We have determined the solution structure of CVB4 2A\n            <jats:sup>pro<\/jats:sup>\n            (extending in an N-terminal direction to include the C-terminal eight residues of CVB4 VP1, which completes the VP1-2A\n            <jats:sup>pro<\/jats:sup>\n            substrate region). In terms of overall fold, it is similar to the crystal structure of the mature human rhinovirus serotype 2 (HRV2) 2A\n            <jats:sup>pro<\/jats:sup>\n            , but the relatively low level (40%) of sequence identity leads to a substantially different surface. We show that differences in the cI-to-eI2 loop between HRV2 and CVB4 2A\n            <jats:sup>pro<\/jats:sup>\n            translate to differences in the mechanism of eIF4GI recognition. Additionally, the nuclear magnetic resonance relaxation properties of CVB4 2A\n            <jats:sup>pro<\/jats:sup>\n            , particularly of residues G1 to S7, F64 to S67, and P107 to G111, reveal that the substrate region is exchanging in and out of a conformation in which it occupies the active site with association and dissociation rates in the range of 100 to 1,000 s\n            <jats:sup>\u22121<\/jats:sup>\n            . This exchange influences the conformation of the active site and points to a mechanism for how self-processing can occur efficiently while product inhibition is avoided.\n          <\/jats:p>","DOI":"10.1128\/jvi.80.3.1451-1462.2006","type":"journal-article","created":{"date-parts":[[2006,1,13]],"date-time":"2006-01-13T13:18:00Z","timestamp":1137158280000},"page":"1451-1462","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":44,"title":["Structure and Dynamics of Coxsackievirus B4 2A Proteinase, an Enyzme Involved in the Etiology of Heart Disease"],"prefix":"10.1128","volume":"80","author":[{"given":"Nicola J.","family":"Baxter","sequence":"first","affiliation":[{"name":"Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Roetzer","sequence":"additional","affiliation":[{"name":"Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Institute of Medical Biochemistry, Medical University of Vienna, Dr. Bohr-Gasse 9\/3, A-1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Dieter","family":"Liebig","sequence":"additional","affiliation":[{"name":"Axon Neuroscience GmbH, Rennweg 95b, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana E.","family":"Sedelnikova","sequence":"additional","affiliation":[{"name":"Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Hounslow","sequence":"additional","affiliation":[{"name":"Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Skern","sequence":"additional","affiliation":[{"name":"Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Institute of Medical Biochemistry, Medical University of Vienna, Dr. Bohr-Gasse 9\/3, A-1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Waltho","sequence":"additional","affiliation":[{"name":"Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"31","volume":"223","year":"1997","unstructured":"Baboonian, C., M. J. Davies, J. C. Booth, and W. J. McKenna. 1997. Coxsackie B viruses and human heart disease. Curr. Top. Microbiol. Immunol.223:31-52.","journal-title":"Curr. Top. Microbiol. 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