{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:08:51Z","timestamp":1789945731794,"version":"4.0.1"},"reference-count":80,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T00:00:00Z","timestamp":1436140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"F.W.O. Vlaanderen","award":["G0E3414N"],"award-info":[{"award-number":["G0E3414N"]}]},{"name":"F.W.O. Vlaanderen","award":["G.0433.12"],"award-info":[{"award-number":["G.0433.12"]}]},{"name":"Inter-University Attraction Poles Program, Belgian State, Belgian Science Policy","award":["IUAP 7\/10"],"award-info":[{"award-number":["IUAP 7\/10"]}]},{"name":"KULeuven","award":["OT\/12\/081"],"award-info":[{"award-number":["OT\/12\/081"]}]},{"name":"FAPESP, The State of S\u00e3o Paulo Research Foundation, post-doc scholarship","award":["2013\/21329-0"],"award-info":[{"award-number":["2013\/21329-0"]}]},{"name":"FAPESP, The State of S\u00e3o Paulo Research Foundation, doctoral scholarship","award":["2013\/21342-7"],"award-info":[{"award-number":["2013\/21342-7"]}]},{"name":"CNPq, The National Council for Scientific and Technological Development","award":["402508\/2012-2"],"award-info":[{"award-number":["402508\/2012-2"]}]},{"name":"Nucleus for Research on Animal Toxins (NAP-TOXAN-USP)","award":["12-125432.1.3"],"award-info":[{"award-number":["12-125432.1.3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The toxin, previously described as a \u201cnon-toxic\u201d toxin, was isolated from the scorpion venom of Tityus serrulatus (Ts), responsible for the most severe and the highest number of accidents in Brazil. In this study, the subtype specificity and selectivity of Ts4 was investigated using six mammalian Nav channels (Nav1.2\u2192Nav1.6 and Nav1.8) and two insect Nav channels (DmNav1 and BgNav). The electrophysiological assays showed that Ts4 specifically inhibited the fast inactivation of Nav1.6 channels, the most abundant sodium channel expressed in the adult central nervous system, and can no longer be classified as a \u201cnon-toxic peptide\u201d. Based on the results, we could classify the Ts4 as a classical \u03b1-toxin. The Ts4 3D-structural model was built based on the solved X-ray Ts1 3D-structure, the major toxin from Ts venom with which it shares high sequence identity (65.57%). The Ts4 model revealed a flattened triangular shape constituted by three-stranded antiparallel \u03b2-sheet and one \u03b1-helix stabilized by four disulfide bonds. The absence of a Lys in the first amino acid residue of the N-terminal of Ts4 is probably the main responsible for its low toxicity. Other key amino acid residues important to the toxicity of \u03b1- and \u03b2-toxins are discussed here.<\/jats:p>","DOI":"10.3390\/toxins7072534","type":"journal-article","created":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T12:21:05Z","timestamp":1436185265000},"page":"2534-2550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Revealing the Function and the Structural Model of Ts4:  Insights into the \u201cNon-Toxic\u201d Toxin from Tityus serrulatus Venom"],"prefix":"10.3390","volume":"7","author":[{"given":"Manuela","family":"Pucca","sequence":"first","affiliation":[{"name":"Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Av. do Caf\u00e9, s\/n, Ribeir\u00e3o Preto, SP 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Cerni","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Av. do Caf\u00e9, s\/n, Ribeir\u00e3o Preto, SP 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-5702","authenticated-orcid":false,"given":"Steve","family":"Peigneur","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology, University of Leuven, O&N 2, Herestraat 49, P.O. Box 922,  Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Bordon","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Av. do Caf\u00e9, s\/n, Ribeir\u00e3o Preto, SP 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tytgat","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology, University of Leuven, O&N 2, Herestraat 49, P.O. Box 922,  Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-6033","authenticated-orcid":false,"given":"Eliane","family":"Arantes","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Av. do Caf\u00e9, s\/n, Ribeir\u00e3o Preto, SP 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,6]]},"reference":[{"key":"ref_1","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_2","first-page":"299","article-title":"Scorpionism and dangerous species of Brazil","volume":"Volume 4","author":"Gopalakrishnakone","year":"2015","journal-title":"Scorpion Venoms"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.bbrc.2008.04.104","article-title":"Tityus serrulatus hypotensins: A new family of peptides from scorpion venom","volume":"371","author":"Silva","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/S0041-0101(01)00122-2","article-title":"A hyaluronidase from Tityus serrulatus scorpion venom: isolation, characterization and inhibition by flavonoids","volume":"39","author":"Pessini","year":"2001","journal-title":"Toxicon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/0041-0101(93)90253-F","article-title":"Peptide T, a novel bradykinin potentiator isolated from Tityus serrulatus scorpion venom","volume":"31","author":"Ferreira","year":"1993","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"920","DOI":"10.2174\/092986609788923329","article-title":"Tityus serrulatus scorpion venom and toxins: An overview","volume":"16","author":"Cologna","year":"2009","journal-title":"Protein Pept. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.toxicon.2014.07.014","article-title":"Molecular and functional characterization of metalloserrulases, new metalloproteases from the Tityus serrulatus venom gland","volume":"90","author":"Carmo","year":"2014","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"210","DOI":"10.4236\/ojgen.2012.24027","article-title":"Transcriptome analysis of the Tityus serrulatus scorpion venom gland","volume":"2","author":"Alvarenga","year":"2012","journal-title":"Open J. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0041-0101(96)00198-5","article-title":"Toxins and genes isolated from scorpions of the genus Tityus","volume":"35","author":"Becerril","year":"1997","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.toxicon.2014.11.233","article-title":"Scorpion venom components as potential candidates for drug development","volume":"93","author":"Ortiz","year":"2015","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1046\/j.1432-1327.1999.00625.x","article-title":"Scorpion toxins specific for Na+-channels","volume":"264","author":"Possani","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.toxicon.2006.09.023","article-title":"Voltage-gated sodium channel modulation by scorpion alpha-toxins","volume":"49","author":"Bosmans","year":"2007","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/molbev\/msp310","article-title":"Positions under positive selection\u2014Key for selectivity and potency of scorpion alpha-toxins","volume":"27","author":"Weinberger","year":"2010","journal-title":"Mol. Biol. Evol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1432-1033.1986.tb09488.x","article-title":"Differential effects of defined chemical modifications on antigenic and pharmacological activities of scorpion alpha and beta toxins","volume":"155","author":"Darbon","year":"1986","journal-title":"Eur. J. Biochem."},{"key":"ref_15","first-page":"411","article-title":"Scorpion venom research around the world: Tityus serrulatus","volume":"Volume 4","author":"Gopalakrishnakone","year":"2015","journal-title":"Scorpion Venoms"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11099","DOI":"10.1016\/S0021-9258(18)60433-8","article-title":"Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and -resistant cells","volume":"264","author":"Singh","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nature07473","article-title":"Deconstructing voltage sensor function and pharmacology in sodium channels","volume":"456","author":"Bosmans","year":"2008","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0165-6147(99)01398-X","article-title":"A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies","volume":"20","author":"Tytgat","year":"1999","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.toxicon.2004.03.022","article-title":"Current views on scorpion toxins specific for K+-channels","volume":"43","author":"Possani","year":"2004","journal-title":"Toxicon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.neuropharm.2015.03.027","article-title":"A gamut of undiscovered electrophysiological effects produced by Tityus serrulatus toxin 1 on Na-type isoforms","volume":"95","author":"Peigneur","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.toxicon.2014.02.010","article-title":"Functional and structural study comparing the C-terminal amidated beta-neurotoxin Ts1 with its isoform Ts1-G isolated from Tityus serrulatus venom","volume":"83","author":"Coelho","year":"2014","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1111\/j.1742-4658.2012.08545.x","article-title":"Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityus serrulatus venom","volume":"279","author":"Cologna","year":"2012","journal-title":"FEBS J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pucca, M.B., Peigneur, S., Cologna, C.T., Cerni, F.A., Zoccal, K.F., Bordon, K.C.F., Faccioli, L.H., Tytgat, J., and Arantes, E.C. (2015). Electrophysiological characterization of the first Tityus serrulatus alpha-like toxin, Ts5: Evidence of a pro-inflammatory toxin on macrophages. Biochimie.","DOI":"10.1016\/j.biochi.2015.04.010"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"892","DOI":"10.3390\/toxins6030892","article-title":"Electrophysiological characterization of Ts6 and Ts7, K+ channel toxins isolated through an improved Tityus serrulatus venom purification procedure","volume":"6","author":"Cerni","year":"2014","journal-title":"Toxins"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.toxicon.2011.05.001","article-title":"Purification and characterization of Ts15, the first member of a new alpha-KTX subfamily from the venom of the Brazilian scorpion Tityus serrulatus","volume":"58","author":"Cologna","year":"2011","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12321","DOI":"10.1074\/jbc.M111.329607","article-title":"New tricks of an old pattern structural versatility of scorpion toxins with common cysteine spacing","volume":"287","author":"Saucedo","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/BF01025013","article-title":"The complete amino acid sequence of toxin TsTX-VI isolated from the venom of the scorpion Tityus serrulatus","volume":"9","author":"Marangoni","year":"1990","journal-title":"J. Protein Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/0041-0101(95)00005-7","article-title":"The scorpion envenoming syndrome","volume":"33","author":"Ismail","year":"1995","journal-title":"Toxicon"},{"key":"ref_29","first-page":"729","article-title":"Isolation of toxin TsTX-VI from Tityus serrulatus scorpion venom. Effects on the release of neurotransmitters from synaptosomes","volume":"39","author":"Sampaio","year":"1996","journal-title":"Biochem. Mol. Biol. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1007\/s00125-003-1159-8","article-title":"Voltage-dependent K+ channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets","volume":"46","author":"MacDonald","year":"2003","journal-title":"Diabetologia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1128\/JB.01049-09","article-title":"The Aromatic Ring of Phenylalanine 334 Is Essential for Oligomerization of Vibrio vulnificus Hemolysin","volume":"192","author":"Kashimoto","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-immunol-031210-101340","article-title":"Nucleic acid recognition by the innate immune system","volume":"29","author":"Barbalat","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/prot.21598","article-title":"Dopamine transporter comparative molecular modeling and binding site prediction using the LeuT(Aa) leucine transporter as a template","volume":"70","author":"Indarte","year":"2008","journal-title":"Proteins-Struct. Funct. Bioinform."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8656","DOI":"10.1128\/JVI.00767-08","article-title":"Structural insight into the human immunodeficiency virus Vif SOCS box and its role in human E3 ubiquitin ligase assembly","volume":"82","author":"Stanley","year":"2008","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cytogfr.2011.02.001","article-title":"Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: Key modulators of innate immune responses to double-stranded RNA viruses","volume":"22","author":"Yu","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/glia.10212","article-title":"Chlorotoxin-sensitive Ca2+-activated Cl-channel in type R2 reactive astrocytes from adult rat brain","volume":"42","author":"Dalton","year":"2003","journal-title":"Glia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbamcr.2011.01.034","article-title":"The pro- and anti-inflammatory properties of the cytokine interleukin-6","volume":"1813","author":"Scheller","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"C361","DOI":"10.1152\/ajpcell.1993.264.2.C361","article-title":"Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion","volume":"264","author":"DeBin","year":"1993","journal-title":"Am. J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1515\/bchm2.1957.306.1-2.269","article-title":"Venoms of the Brazilian scorpions Tityus serrulatus and Tityus bahiensis","volume":"306","author":"Fischer","year":"1957","journal-title":"Hoppe Seylers Z. Physiol. Chem."},{"key":"ref_40","first-page":"1","article-title":"Effects of a toxin present in a purified extract of telsons from the scorpion Tityus serrulatus on smooth muscle preparations and in mice","volume":"121","author":"Diniz","year":"1959","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_41","first-page":"899","article-title":"Separation of toxic components from the brazillian scorpion Tityus serrulatus venom","volume":"33","author":"Gomez","year":"1966","journal-title":"Mem. Inst. Butantan."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/0041-0101(89)90102-5","article-title":"A simplified procedure for the fractionation of Tityus serrulatus venom: Isolation and partial characterization of TsTX-IV, a new neurotoxin","volume":"27","author":"Arantes","year":"1989","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0041-0101(98)00187-1","article-title":"Molecular cloning and genomic analysis of TsNTxp: an immunogenic protein from Tityus serrulatus scorpion venom","volume":"37","author":"Guatimosim","year":"1999","journal-title":"Toxicon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0041-0101(01)00197-0","article-title":"Induction of neutralizing antibodies against Tityus serrulatus scorpion toxins by immunization with a mixture of defined synthetic epitopes","volume":"40","author":"Alvarenga","year":"2002","journal-title":"Toxicon"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0041-0101(97)00103-7","article-title":"In vivo protection against Tityus serrulatus scorpion toxins by immunization of mice with a non-toxic protein","volume":"36","author":"Kalapothakis","year":"1998","journal-title":"Toxicon"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/S0161-5890(01)00117-1","article-title":"Molecular basis for the cross-reactivity of antibodies elicited by a natural anatoxin with alpha- and beta-toxins from the venom of Tityus serrulatus scorpion","volume":"38","author":"Molina","year":"2002","journal-title":"Mol. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0041-0101(96)00133-X","article-title":"Neutralizing capacity of antibodies elicited by a non-toxic protein purified from the venom of the scorpion Tityus serrulatus","volume":"35","author":"Kalapothakis","year":"1997","journal-title":"Toxicon"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1007\/s11095-008-9782-1","article-title":"Maurocalcine as a non toxic drug carrier overcomes doxorubicin resistance in the cancer cell line MDA-MB 231","volume":"26","author":"Aroui","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0041-0101(03)00008-4","article-title":"Purification and primary structure determination of Tf4, the first bioactive peptide isolated from the venom of the Brazilian scorpion Tityus fasciolatus","volume":"41","author":"Wagner","year":"2003","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1146\/annurev.physiol.63.1.871","article-title":"Resurgence of sodium channel research","volume":"63","author":"Goldin","year":"2001","journal-title":"Annu. Rev. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1152\/jn.00383.2013","article-title":"Evidence for a role of Nav1.6 in facilitating increases in neuronal hyperexcitability during epileptogenesis","volume":"110","author":"Hargus","year":"2013","journal-title":"J. Neurophysiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nrn1430","article-title":"The neurobiology of antiepileptic drugs","volume":"5","author":"Rogawski","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1001\/archneur.61.8.1294","article-title":"Epilepsy due to a destructive brain lesion caused by a scorpion sting","volume":"61","author":"Bonilha","year":"2004","journal-title":"Arch. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/B978-0-444-52891-9.00048-8","article-title":"Modes of onset of epilepsy and differential diagnosis","volume":"111","author":"Peter","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1021\/jm00180a022","article-title":"Relationship of octanol\/water partition coefficient and molecular weight to rat brain capillary permeability","volume":"23","author":"Levin","year":"1980","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1602\/neurorx.2.4.541","article-title":"Medicinal chemical properties of successful central nervous system drugs","volume":"2","author":"Pajouhesh","year":"2005","journal-title":"NeuroRx"},{"key":"ref_57","first-page":"5","article-title":"Impacts of blood-brain barrier in drug delivery and targeting of brain tumors","volume":"2","author":"Omidi","year":"2012","journal-title":"Bioimpacts"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/bip.22257","article-title":"From venoms to BBB shuttles: Synthesis and blood-brain barrier transport assessment of apamin and a nontoxic analog","volume":"100","author":"Teixido","year":"2013","journal-title":"Biopolymers"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4587","DOI":"10.1021\/nn1008512","article-title":"Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma","volume":"4","author":"Kievit","year":"2010","journal-title":"ACS Nano"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e88174","DOI":"10.1371\/journal.pone.0088174","article-title":"TLR2, TLR4 and CD14 recognize venom-associated molecular patterns from Tityus serrulatus to induce macrophage-derived inflammatory mediators","volume":"9","author":"Zoccal","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.toxicon.2011.04.017","article-title":"Tityus serrulatus venom and toxins Ts1, Ts2 and Ts6 induce macrophage activation and production of immune mediators","volume":"57","author":"Zoccal","year":"2011","journal-title":"Toxicon"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxicon.2012.10.002","article-title":"Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms dependent on lipid mediators and cytokine production","volume":"61","author":"Zoccal","year":"2013","journal-title":"Toxicon"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Petricevich, V.L. (2010). Scorpion venom and the inflammatory response. Mediat. Inflamm.","DOI":"10.1155\/2010\/903295"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/09629350210308","article-title":"Effect of Tityus serrulatus venom on cytokine production and the activity of murine macrophages","volume":"11","author":"Petricevich","year":"2002","journal-title":"Mediat. Inflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-2249.2008.03754.x","article-title":"Macrophage activation, phagocytosis and intracellular calcium oscillations induced by scorpion toxins from Tityus serrulatus","volume":"154","author":"Petricevich","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7822","DOI":"10.4049\/jimmunol.178.12.7822","article-title":"Expression of the voltage-gated sodium channel NaV1.5 in the macrophage late endosome regulates endosomal acidification","volume":"178","author":"Carrithers","year":"2007","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Cha\u00efr-Yousfi, I., Laraba-Djebari, F., and Hammoudi-Triki, D. (2015). Androctonus australis hector venom contributes to the interaction between 2 neuropeptides and mast cells in pulmonary hyperresponsiveness. Int. Immunopharmacol.","DOI":"10.1016\/j.intimp.2015.01.008"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/(SICI)1097-0134(199707)28:3<360::AID-PROT6>3.0.CO;2-G","article-title":"Refined solution structure of the anti-mammal and anti-insect LqqIII scorpion toxin: comparison with other scorpion toxins","volume":"28","author":"Landon","year":"1997","journal-title":"Proteins"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1006\/jmbi.1996.0473","article-title":"Crystal structure of an acidic neurotoxin from scorpion Buthus martensii Karsch at 1.85 A resolution","volume":"261","author":"Li","year":"1996","journal-title":"J. Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0968-0004(81)90105-5","article-title":"Architecture of Scorpion Neurotoxins\u2014A class of membrane-binding proteins","volume":"6","author":"Fontecillacamps","year":"1981","journal-title":"Trends Biochem. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1042\/bj2290739","article-title":"Scorpion toxins from Centruroides noxius and Tityus serrulatus. Primary structures and sequence comparison by metric analysis","volume":"229","author":"Possani","year":"1985","journal-title":"Biochem. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0041-0101(90)90295-I","article-title":"Structure-activity relationships of scorpion alpha-neurotoxins: contribution of arginine residues","volume":"28","author":"Kharrat","year":"1990","journal-title":"Toxicon"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1399-3011.1983.tb02084.x","article-title":"Alpha-scorpion neurotoxin derivatives suitable as potential markers of sodium channels. Preparation and characterization","volume":"22","author":"Darbon","year":"1983","journal-title":"Int. J. Pept. Protein Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1107\/S090744490202111X","article-title":"Structural analysis of Tityus serrulatus Ts1 neurotoxin at atomic resolution: Insights into interactions with Na+ channels","volume":"59","author":"Pinheiro","year":"2003","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.coi.2011.03.001","article-title":"Regulation of innate and adaptive immunity by the commensal microbiota","volume":"23","author":"Jarchum","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.toxicon.2010.11.017","article-title":"A portable device for the electrical extraction of scorpion venom","volume":"57","author":"Lowe","year":"2011","journal-title":"Toxicon"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1432-1033.1967.tb00047.x","article-title":"A protein sequenator","volume":"1","author":"Edman","year":"1967","journal-title":"Eur. J. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/0896-6273(92)90239-A","article-title":"Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs","volume":"9","author":"Liman","year":"1992","journal-title":"Neuron"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0896-6273(90)90442-I","article-title":"Gating mechanism of a cloned potassium channel expressed in frog oocytes and mammalian cells","volume":"4","author":"Koren","year":"1990","journal-title":"Neuron"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1006\/jmbi.1999.2868","article-title":"Crystal structure of neurotoxin Ts1 from Tityus serrulatus provides insights into the specificity and toxicity of scorpion toxins","volume":"290","author":"Polikarpov","year":"1999","journal-title":"J. Mol. Biol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/7\/2534\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:48:46Z","timestamp":1760215726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/7\/2534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,6]]},"references-count":80,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2015,7]]}},"alternative-id":["toxins7072534"],"URL":"https:\/\/doi.org\/10.3390\/toxins7072534","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,6]]}}}