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dc.contributor.authorSikorra, Stefan
dc.contributor.authorSkiba, Martin
dc.contributor.authorDorner, Martin B
dc.contributor.authorWeisemann, Jasmin
dc.contributor.authorWeil, Mirjam
dc.contributor.authorValdezate, Sylvia 
dc.contributor.authorDavletov, Bazbek
dc.contributor.authorRummel, Andreas
dc.contributor.authorDorner, Brigitte G
dc.contributor.authorBinz, Thomas
dc.date.accessioned2020-04-29T07:36:45Z
dc.date.available2020-04-29T07:36:45Z
dc.date.issued2018
dc.identifier.citationToxins (Basel). 2018 Aug 1;10(8). pii: E311.es_ES
dc.identifier.issn2072-6651es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9796
dc.description.abstractIn the recent past, about 40 botulinum neurotoxin (BoNT) subtypes belonging to serotypes A, B, E, and F pathogenic to humans were identified among hundreds of independent isolates. BoNTs are the etiological factors of botulism and represent potential bioweapons; however, they are also recognized pharmaceuticals for the efficient counteraction of hyperactive nerve terminals in a variety of human diseases. The detailed biochemical characterization of subtypes as the basis for development of suitable countermeasures and possible novel therapeutic applications is lagging behind the increase in new subtypes. Here, we report the primary structure of a ninth subtype of BoNT/F. Its amino-acid sequence diverges by at least 8.4% at the holotoxin and 13.4% at the enzymatic domain level from all other known BoNT/F subtypes. We found that BoNT/F9 shares the scissile Q58/K59 bond in its substrate vesicle associated membrane protein 2 with the prototype BoNT/F1. Comparative biochemical analyses of four BoNT/F enzymatic domains showed that the catalytic efficiencies decrease in the order F1 > F7 > F9 > F6, and vary by up to a factor of eight. KM values increase in the order F1 > F9 > F6 ≈ F7, whereas kcat decreases in the order F7 > F1 > F9 > F6. Comparative substrate scanning mutagenesis studies revealed a unique pattern of crucial substrate residues for each subtype. Based upon structural coordinates of F1 bound to an inhibitor polypeptide, the mutational analyses suggest different substrate interactions in the substrate binding channel of each subtype.es_ES
dc.description.sponsorshipThis research was funded by Deutsche Forschungsgemeinschaft, grant number Bi 660/3-1, to T.B., by Swiss Federal Department of Defence, Civil Protection and Sport, grant number 353003364/Stm, and by the Federal Ministry of Education and Research, grant number 031L0111A, TiViBoNT, to B.G.D. The APC was funded by Hannover Medical School, Hannover, Germany.es_ES
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectClostridium botulinumes_ES
dc.subjectZn2+ proteasees_ES
dc.subjectBotulinum neurotoxines_ES
dc.subjectSerotype Fes_ES
dc.subjectSubtypees_ES
dc.subjectSynaptobrevines_ES
dc.subjectVesicle associated membrane protein 2 (VAMP-2)es_ES
dc.subject.meshBotulinum Toxins es_ES
dc.subject.meshCatalysis es_ES
dc.subject.meshPeptides es_ES
dc.subject.meshSubstrate Specificity es_ES
dc.subject.meshVesicle-Associated Membrane Protein 2 es_ES
dc.titleBotulinum Neurotoxin F Subtypes Cleaving the VAMP-2 Q58⁻K59 Peptide Bond Exhibit Unique Catalytic Properties and Substrate Specificitieses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30071628es_ES
dc.format.volume10es_ES
dc.format.number8es_ES
dc.format.page311es_ES
dc.identifier.doi10.3390/toxins10080311es_ES
dc.contributor.funderDeutsche Forschungsgemeinschaft (Alemania) 
dc.contributor.funderFederal Ministry of Education & Research (Alemania) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2072-6651es_ES
dc.relation.publisherversionhttps://doi.org/10.3390/toxins10080311es_ES
dc.identifier.journalToxinses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ Bi 660/3-1es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ 353003364/Stmes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/031L0111Aes_ES
dc.rights.accessRightsopen accesses_ES


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