{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:22:20Z","timestamp":1791638540867,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"CONAHCYT (Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas)","doi-asserted-by":"publisher","award":["303045"],"award-info":[{"award-number":["303045"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"CONAHCYT (Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas)","doi-asserted-by":"publisher","award":["IN200323"],"award-info":[{"award-number":["IN200323"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Direcci\u00f3n General de Asuntos de Personal Acad\u00e9mico\u2013UNAM","award":["303045"],"award-info":[{"award-number":["303045"]}]},{"name":"Direcci\u00f3n General de Asuntos de Personal Acad\u00e9mico\u2013UNAM","award":["IN200323"],"award-info":[{"award-number":["IN200323"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Five peptides were isolated from the venom of the Mexican scorpion Centruroides bonito by chromatographic procedures (molecular weight sieving, ion exchange columns, and HPLC) and were denoted Cbo1 to Cbo5. The first four peptides contain 66 amino acid residues and the last one contains 65 amino acids, stabilized by four disulfide bonds, with a molecular weight spanning from about 7.5 to 7.8 kDa. Four of them are toxic to mice, and their function on human Na+ channels expressed in HEK and CHO cells was verified. One of them (Cbo5) did not show any physiological effects. The ones toxic to mice showed that they are modifiers of the gating mechanism of the channels and belong to the beta type scorpion toxin (\u03b2-ScTx), affecting mainly the Nav1.6 channels. A phylogenetic tree analysis of their sequences confirmed the high degree of amino acid similarities with other known bona fide \u03b2-ScTx. The envenomation caused by this venom in mice is treated by using commercially horse antivenom available in Mexico. The potential neutralization of the toxic components was evaluated by means of surface plasmon resonance using four antibody fragments (10FG2, HV, LR, and 11F) which have been developed by our group. These antitoxins are antibody fragments of single-chain antibody type, expressed in E. coli and capable of recognizing Cbo1 to Cbo4 toxins to various degrees.<\/jats:p>","DOI":"10.3390\/toxins16030125","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T03:31:23Z","timestamp":1709263883000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of Sodium Channel Peptides Obtained from the Venom of the Scorpion Centruroides bonito"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-5303","authenticated-orcid":false,"given":"Rita","family":"Restano-Cassulini","sequence":"first","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timoteo","family":"Olamendi-Portugal","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2531-9232","authenticated-orcid":false,"given":"Lidia","family":"Ria\u00f1o-Umbarila","sequence":"additional","affiliation":[{"name":"Investigadora por M\u00e9xico CONAHCYT, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62250, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Z.","family":"Zamudio","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-9269","authenticated-orcid":false,"given":"Gustavo","family":"Delgado-Prudencio","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-8029","authenticated-orcid":false,"given":"Baltazar","family":"Becerril","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-2661","authenticated-orcid":false,"given":"Lourival D.","family":"Possani","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"ref_1","unstructured":"Rein, J.O. (2023). The Scorpion Files, NTNU."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.actatropica.2008.05.021","article-title":"Epidemiology of scorpionism: A global appraisal","volume":"107","author":"Chippaux","year":"2008","journal-title":"Acta Trop."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00134-020-05924-8","article-title":"Scorpion envenomation: State of the art","volume":"46","author":"Abroug","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_4","first-page":"349","article-title":"Scorpionism in the old world","volume":"Volume 3","author":"Buckley","year":"1971","journal-title":"Venomous Animal and Their Venoms"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0041-0101(97)00099-8","article-title":"Comparison and characterization of the venoms of three Parabuthus scorpion species occurring in southern Africa","volume":"36","author":"Debont","year":"1998","journal-title":"Toxicon Off. J. Int. Soc. Toxinol."},{"key":"ref_6","unstructured":"Keegan, H.L., and Macfarlane, W.V. (1963). Venomous and Poisonous Animals and Noxious Plants of the Pacific Region: A Collection of Papers Based on a Symposium in the Public Health and Medical Science Division at the Tenth Pacific Science Congress, Macmillan."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bettini, S. (1978). Arthropod Venoms. Handbuch der Experimentellen Pharmakologie, Springer. [1st ed.].","DOI":"10.1007\/978-3-642-45501-8"},{"key":"ref_8","unstructured":"Rosenber, P. (1978). Toxins: Animal, Plant and Microbial, Pergamon Press."},{"key":"ref_9","first-page":"16","article-title":"Elemental analysis of scorpion venoms","volume":"7","author":"Kunnathodi","year":"2016","journal-title":"J. Venom Res."},{"key":"ref_10","unstructured":"Bettini, S. (1978). Handbook of Experimental Physiology, Springer."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/BF00582392","article-title":"Effect of toxins isolated from the venom of the scorpion Centruroides sculpturatus on the Na currents of the node of Ranvier","volume":"393","author":"Meves","year":"1982","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1146\/annurev.pa.20.040180.000311","article-title":"Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes","volume":"20","author":"Catterall","year":"1980","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1016\/S0021-9258(17)33092-2","article-title":"Purification of a toxic protein from scorpion venom which activates the action potential Na+ ionophore","volume":"251","author":"Catterall","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/0005-2736(80)90230-8","article-title":"Potential-dependent interaction of toxin from venom of the scorpion Buthus eupeus with sodium channels in myelinated fibre: Voltage clamp experiments","volume":"597","author":"Mozhayeva","year":"1980","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8034","DOI":"10.1074\/jbc.271.14.8034","article-title":"Scorpion toxins affecting sodium current inactivation bind to distinct homologous receptor sites on rat brain and insect sodium channels","volume":"271","author":"Gordon","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12553","DOI":"10.1016\/S0021-9258(18)33546-4","article-title":"Tityus serrulatus venom contains two classes of toxins. Tityus gamma toxin is a new tool with a very high affinity for studying the Na+ channel","volume":"257","author":"Barhanin","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mendes, L.C., Viana, G.M.M., Nencioni, A.L.A., Pimenta, D.C., and Beraldo-Neto, E. (2023). Scorpion Peptides and Ion Channels: An Insightful Review of Mechanisms and Drug Development. Toxins, 15.","DOI":"10.3390\/toxins15040238"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1093\/sysbio\/syac021","article-title":"Phylogenomics of Scorpions Reveal Contemporaneous Diversification of Scorpion Mammalian Predators and Mammal-Active Sodium Channel Toxins","volume":"71","author":"Aharon","year":"2022","journal-title":"Syst. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Santibanez-Lopez, C.E., Francke, O.F., Ureta, C., and Possani, L.D. (2015). Scorpions from Mexico: From Species Diversity to Venom Complexity. Toxins, 8.","DOI":"10.3390\/toxins8010002"},{"key":"ref_20","first-page":"25","article-title":"A new Centruroides Marx, 1890 (Scorpiones, Buthidae) from Southern Guerrero State, Mexico","volume":"28","author":"Teruel","year":"2016","journal-title":"Rev. Ib\u00e9rica Aracnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.actatropica.2018.08.002","article-title":"North American scorpion species of public health importance with a reappraisal of historical epidemiology","volume":"187","author":"Possani","year":"2018","journal-title":"Acta Trop."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0305-0491(88)90277-5","article-title":"Isolation and characterization of two toxins from the Mexican scorpion Centruroides limpidus limpidus Karsch","volume":"89","author":"Alagon","year":"1988","journal-title":"Comp. Biochem. Physiol. B Comp. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0305-0491(95)02031-4","article-title":"Structural and functional comparison of toxins from the venom of the scorpions Centruroides infamatus infamatus, Centruroides limpidus limpidus and Centruroides noxius","volume":"113","author":"Ramirez","year":"1996","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Garcia-Villalvazo, P.E., Jimenez-Vargas, J.M., Lino-Lopez, G.J., Meneses, E.P., Bermudez-Guzman, M.J., Barajas-Saucedo, C.E., Delgado Enciso, I., Possani, L.D., and Valdez-Velazquez, L.L. (2023). Unveiling the Protein Components of the Secretory-Venom Gland and Venom of the Scorpion Centruroides possanii (Buthidae) through Omic Technologies. Toxins, 15.","DOI":"10.3390\/toxins15080498"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.toxicon.2019.11.004","article-title":"Biochemical characterization of the venom from the Mexican scorpion Centruroides ornatus, a dangerous species to humans","volume":"173","author":"Zamudio","year":"2020","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.toxicon.2020.05.021","article-title":"Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico","volume":"184","author":"Possani","year":"2020","journal-title":"Toxicon Off. J. Int. Soc. Toxinol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Valencia-Martinez, H., Olamendi-Portugal, T., Restano-Cassulini, R., Serrano-Posada, H., Zamudio, F., Possani, L.D., Riano-Umbarila, L., and Becerril, B. (2022). Characterization of Four Medically Important Toxins from Centruroides huichol Scorpion Venom and Its Neutralization by a Single Recombinant Antibody Fragment. Toxins, 14.","DOI":"10.3390\/toxins14060369"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.toxicon.2020.06.011","article-title":"The three-dimensional structure of the toxic peptide Cl13 from the scorpion Centruroides limpidus","volume":"184","author":"Becerril","year":"2020","journal-title":"Toxicon Off. J. Int. Soc. Toxinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0003-9861(75)90371-9","article-title":"Amino acid sequence of neurotoxin I from Centruroides sculpturatus Ewing","volume":"166","author":"Babin","year":"1975","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_30","first-page":"919","article-title":"Voltage sensor-trapping: Enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II","volume":"21","author":"Cestele","year":"1998","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.molimm.2021.07.010","article-title":"The venom of the scorpion Centruroides limpidus, which causes the highest number of stings in Mexico, is neutralized by two recombinant antibody fragments","volume":"137","author":"Becerril","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6143","DOI":"10.1074\/jbc.M110.189175","article-title":"Exploiting cross-reactivity to neutralize two different scorpion venoms with one single chain antibody fragment","volume":"286","author":"Corzo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Riano-Umbarila, L., Gomez-Ramirez, I.V., Ledezma-Candanoza, L.M., Olamendi-Portugal, T., Rodriguez-Rodriguez, E.R., Fernandez-Taboada, G., Possani, L.D., and Becerril, B. (2019). Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms. Toxins, 11.","DOI":"10.3390\/toxins11010032"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rendon-Anaya, M., Delaye, L., Possani, L.D., and Herrera-Estrella, A. (2012). Global transcriptome analysis of the scorpion Centruroides noxius: New toxin families and evolutionary insights from an ancestral scorpion species. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043331"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/0041-0101(95)00058-T","article-title":"Cloning and characterization of the cDNAs encoding Na+ channel-specific toxins 1 and 2 of the scorpion Centruroides noxius Hoffmann","volume":"33","author":"Vazquez","year":"1995","journal-title":"Toxicon Off. J. Int. Soc. Toxinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.toxicon.2016.04.046","article-title":"Comprehensive analysis of venom from the scorpion Centruroides tecomanus reveals compounds with antimicrobial, cytotoxic, and insecticidal activities","volume":"118","author":"Dobrovinskaya","year":"2016","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29538","DOI":"10.1038\/srep29538","article-title":"Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami","volume":"6","author":"Herzig","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1002\/1873-3468.13530","article-title":"Scorpion toxins interact with nicotinic acetylcholine receptors","volume":"593","author":"Kasheverov","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.peptides.2016.11.008","article-title":"Functional and immuno-reactive characterization of a previously undescribed peptide from the venom of the scorpion Centruroides limpidus","volume":"87","author":"Becerril","year":"2017","journal-title":"Peptides"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.3389\/fimmu.2019.01598","article-title":"History of Envenoming Therapy and Current Perspectives","volume":"10","author":"Pucca","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.toxicon.2014.11.001","article-title":"Phage display as a novel promising antivenom therapy: A review","volume":"93","author":"Roncolato","year":"2015","journal-title":"Toxicon Off. J. Int. Soc. Toxinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.1007\/s00253-023-12578-1","article-title":"Production of recombinant scorpion antivenoms in E. coli: Current state and perspectives","volume":"107","author":"Bideaux","year":"2023","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"giac048","DOI":"10.1093\/gigascience\/giac048","article-title":"Modern venomics-Current insights, novel methods, and future perspectives in biological and applied animal venom research","volume":"11","author":"Anderluh","year":"2022","journal-title":"Gigascience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/01621459.1948.10483254","article-title":"A Method for Obtaining and Analyzing Sensitivity Data","volume":"43","author":"Dixon","year":"1948","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Shakeel, K., Olamendi-Portugal, T., Naseem, M.U., Becerril, B., Zamudio, F.Z., Delgado-Prudencio, G., Possani, L.D., and Panyi, G. (2023). Of Seven New K(+) Channel Inhibitor Peptides of Centruroides bonito, alpha-KTx 2.24 Has a Picomolar Affinity for Kv1.2. Toxins, 15.","DOI":"10.3390\/toxins15080506"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., and Madden, T.L. (2009). BLAST+: Architecture and applications. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-421"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/sysbio\/sys029","article-title":"MrBayes 3.2: Efficient Bayesian phylogenetic inference and model choice across a large model space","volume":"61","author":"Ronquist","year":"2012","journal-title":"Syst. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/oxfordjournals.molbev.a003851","article-title":"A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach","volume":"18","author":"Whelan","year":"2001","journal-title":"Mol. Biol. Evol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.2144\/00286ir01","article-title":"The sequence manipulation suite: JavaScript programs for analyzing and formatting protein and DNA sequences","volume":"28","author":"Stothard","year":"2000","journal-title":"Biotechniques"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20326","DOI":"10.1074\/jbc.M600565200","article-title":"Resurgent current and voltage sensor trapping enhanced activation by a beta-scorpion toxin solely in Nav1.6 channel. Significance in mice Purkinje neurons","volume":"281","author":"Schiavon","year":"2006","journal-title":"J. Biol. Chem."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/3\/125\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:07:37Z","timestamp":1760105257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/3\/125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,1]]},"references-count":51,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["toxins16030125"],"URL":"https:\/\/doi.org\/10.3390\/toxins16030125","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,1]]}}}