{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:19:00Z","timestamp":1788297540367,"version":"build-2803163510"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Biological Macromolecules"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.ijbiomac.2020.08.163","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T10:01:14Z","timestamp":1598176874000},"page":"2953-2963","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Blocking of negative charged carboxyl groups converts Naja atra neurotoxin to cardiotoxin-like protein"],"prefix":"10.1016","volume":"164","author":[{"given":"Yi-Jun","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Ting","family":"Chiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Chin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Jung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Sen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0005","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.toxicon.2010.07.010","article-title":"Structure, function and evolution of three-finger toxins: mini proteins with multiple targets","volume":"56","author":"Kini","year":"2010","journal-title":"Toxicon"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0010","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/jnc.13975","article-title":"The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions","volume":"142","author":"Kessler","year":"2017","journal-title":"J. Neurochem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0015","doi-asserted-by":"crossref","first-page":"E474","DOI":"10.3390\/toxins10110474","article-title":"Snake venom peptides: tools of biodiscovery","volume":"10","author":"Munawar","year":"2018","journal-title":"Toxins"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0020","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4331\/wjbc.v10.i1.17","article-title":"Last decade update for three-finger toxins: newly emerging structures and biological activities","volume":"10","author":"Utkin","year":"2019","journal-title":"World J. Biol. Chem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0025","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3389\/fevo.2019.00218","article-title":"Multifunctional toxins in snake venoms and therapeutic implications: from pain to hemorrhage and necrosis","volume":"7","author":"Ferraz","year":"2019","journal-title":"Front. Ecol. Evol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0030","doi-asserted-by":"crossref","first-page":"9362","DOI":"10.1074\/jbc.270.16.9362","article-title":"Genetic engineering of snake toxins. The functional site of erabutoxin a, as delineated by site-directed mutagenesis, includes variant residues","volume":"270","author":"Tr\u00e9meau","year":"1995","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0035","doi-asserted-by":"crossref","first-page":"34851","DOI":"10.1074\/jbc.274.49.34851","article-title":"Variability among the sites by which curaremimetic toxins bind to Torpedo acetylcholine receptor, as revealed by identification of the functional residues of \u03b1-cobratoxin","volume":"274","author":"Antil","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0040","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/jccs.199900048","article-title":"Biochemistry and molecular biology of snake neurotoxin","volume":"46","author":"Yang","year":"1999","journal-title":"J. Chin. Chem. Soc."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0045","doi-asserted-by":"crossref","first-page":"29594","DOI":"10.1074\/jbc.M909746199","article-title":"Molecular determinants by which a long chain toxin from snake venom interacts with the neuronal \u03b17 nicotinic acetylcholine receptor","volume":"275","author":"Antil-Delbeke","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0050","doi-asserted-by":"crossref","first-page":"3502","DOI":"10.1074\/jbc.272.6.3502","article-title":"Expression and activity of mutants of fasciculin, a peptidic acetylcholinesterase inhibitor from mamba venom","volume":"272","author":"Marchot","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0055","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/protein\/13.3.217","article-title":"Chemical engineering of a three-fingered toxin with anti-\u03b17 neuronal acetylcholine receptor activity","volume":"13","author":"Mourier","year":"2000","journal-title":"Protein Eng."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0060","doi-asserted-by":"crossref","first-page":"18302","DOI":"10.1074\/jbc.275.24.18302","article-title":"Do structural deviations between toxins adopting the same fold reflect functional differences?","volume":"275","author":"Ricciardi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0065","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0039166","article-title":"Engineering of three-finger fold toxins creates ligands with original pharmacological profiles for muscarinic and adrenergic receptors","volume":"7","author":"Fruchart-Gaillard","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0070","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1073\/pnas.1310811111","article-title":"Stability-activity tradeoffs constrain the adaptive evolution of RubisCO","volume":"111","author":"Studer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0075","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jbiosc.2019.03.017","article-title":"Activity-stability trade-off in random mutant proteins","volume":"128","author":"Kurahashi","year":"2019","journal-title":"J. Biosci. Bioeng."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0080","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1006\/bbrc.1997.7549","article-title":"Genomic structures of cardiotoxin 4 and cobrotoxin from Naja naja atra (Taiwan cobra)","volume":"239","author":"Chang","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0085","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1023\/B:BIGI.0000043955.35906.c2","article-title":"Molecular cloning and evolution of the genes encoding the precursors of Taiwan cobra cardiotoxin and cardiotoxin-like basic protein","volume":"42","author":"Chang","year":"2004","journal-title":"Biochem. Genet."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0090","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.toxicon.2007.06.011","article-title":"The mechanism of cytotoxicity by Naja naja atra cardiotoxin 3 is physically distant from its membrane-damaging effect","volume":"50","author":"Chen","year":"2007","journal-title":"Toxicon"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0095","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.toxicon.2011.04.021","article-title":"Membrane-damaging activity of Taiwan cobra cardiotoxin 3 is responsible for its bactericidal activity","volume":"58","author":"Chen","year":"2011","journal-title":"Toxicon"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0100","doi-asserted-by":"crossref","first-page":"E527","DOI":"10.3390\/toxins11090527","article-title":"Naja atra cardiotoxin 3 elicits autophagy and apoptosis in U937 human leukemia cells through the Ca2+\/PP2A\/AMPK axis","volume":"11","author":"Chiou","year":"2019","journal-title":"Toxins"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0105","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-4419-6327-7_12","article-title":"Role of heparan sulfates and glycosphingolipids in the pore formation of basic polypeptides of cobra cardiotoxin","volume":"677","author":"Wu","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0110","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s00894-016-3113-y","article-title":"Putative membrane lytic sites of P-type and S-type cardiotoxins from snake venoms as probed by all-atom molecular dynamics simulations","volume":"22","author":"Gorai","year":"2016","journal-title":"J. Mol. Model."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0115","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1021\/acs.jcim.7b00395","article-title":"Cardiotoxins: functional role of local conformational changes","volume":"57","author":"Konshina","year":"2017","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0120","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0300-9084(90)90121-V","article-title":"Do cardiotoxins possess a functional site? Structural and chemical modification studies reveal the functional site of the cardiotoxin from Naja nigricollis","volume":"72","author":"M\u00e9nez","year":"1990","journal-title":"Biochimie"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0125","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1006\/taap.1996.0162","article-title":"Chemical modification of methionines in a cobra venom cytotoxin differentiates between lytic and binding domains","volume":"139","author":"Stevens-Truss","year":"1996","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0130","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3390\/toxins9010024","article-title":"Detection of Naja atra cardiotoxin using adenosine-based molecular beacon","volume":"9","author":"Shi","year":"2017","journal-title":"Toxins"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0135","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.ijbiomac.2019.06.066","article-title":"Naja atra cardiotoxins enhance the protease activity of chymotrypsin","volume":"136","author":"Shi","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0140","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.abb.2014.10.001","article-title":"Bovine serum albumin with glycated carboxyl groups shows membrane-perturbing activities","volume":"564","author":"Yang","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0145","series-title":"Principles of Fluorescence Spectroscopy","author":"Lakowicz","year":"1999"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0150","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2020.115013","article-title":"Arsenic trioxide-induced p38 MAPK- and Akt-mediated MCL1 downregulation causes apoptosis of BCR-ABL1-positive leukemia cells","volume":"397","author":"Huang","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0155","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1399-3011.1995.tb01334.x","article-title":"Role of amino and carboxyl groups of cobrotoxin in the conformational stability and the interaction with acetylcholine receptor","volume":"46","author":"Kuo","year":"1995","journal-title":"Int. J. Pept. Protein Res."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0160","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3390\/ijms18030520","article-title":"Ovalbumin with glycated carboxyl groups shows membrane-damaging activity","volume":"18","author":"Tang","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0165","series-title":"Lipid Biochemistry","author":"Gurr","year":"2002"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0170","doi-asserted-by":"crossref","first-page":"E262","DOI":"10.3390\/toxins12040262","article-title":"Status of Asp29 and Asp40 in the interaction of Naja atra cardiotoxins with lipid bilayers","volume":"12","author":"Wu","year":"2020","journal-title":"Toxins"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0175","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3109\/09687689509027506","article-title":"The use of fluoresceinphosphatidylethanolamine (FPE) as a real-time probe for peptide-membrane interactions","volume":"12","author":"Wall","year":"1995","journal-title":"Mol. Membr. Biol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0180","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.toxicon.2009.07.032","article-title":"Roles of lysine residues and N-terminal \u03b1-amino group in membrane-damaging activity of Taiwan cobra cardiotoxin 3 toward anionic and zwitterionic phospholipid vesicles","volume":"55","author":"Chiou","year":"2010","journal-title":"Toxicon"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0185","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/72697","article-title":"A colorimetric assay for rapid screening of antimicrobial peptides","volume":"18","author":"Kolusheva","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0190","doi-asserted-by":"crossref","first-page":"14473","DOI":"10.1016\/S0021-9258(17)36647-4","article-title":"Two distinct types of cardiotoxin as revealed by the structure and activity relationship of their interaction with zwitterionic phospholipid dispersions","volume":"269","author":"Chien","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0195","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1016\/S0006-3495(98)77682-9","article-title":"Effect of D57N mutation on membrane activity and molecular unfolding of cobra cardiotoxin","volume":"75","author":"Lo","year":"1998","journal-title":"Biophys. J."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0200","doi-asserted-by":"crossref","first-page":"8413","DOI":"10.1021\/bi9707133","article-title":"Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol\/water mixtures back to water","volume":"36","author":"Luo","year":"1997","journal-title":"Biochemistry"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0205","doi-asserted-by":"crossref","first-page":"12179","DOI":"10.1073\/pnas.182199699","article-title":"Mechanism by which 2,2,2-trifluoroethanol\/water mixtures stabilize secondary-structure formation in peptides: a molecular dynamics study","volume":"99","author":"Roccatano","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0210","doi-asserted-by":"crossref","first-page":"8527","DOI":"10.1021\/bi9723111","article-title":"Solution structure of the cytoplasmic domain of the human CD4 glycoprotein by CD and 1H NMR spectroscopy: implications for biological functions","volume":"37","author":"Wray","year":"1998","journal-title":"Biochemistry"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0215","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0014-5793(99)00653-5","article-title":"The structural flexibility of the preferredoxin transit peptide","volume":"453","author":"Wienk","year":"1999","journal-title":"FEBS Lett."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0220","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3390\/biom8030077","article-title":"Membrane active peptides and their biophysical characterization","volume":"8","author":"Avci","year":"2018","journal-title":"Biomolecules"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0225","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0006-3495(02)75156-4","article-title":"Interaction of cardiotoxins with membranes: a molecular modeling study","volume":"83","author":"Efremov","year":"2002","journal-title":"Biophys. J."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0230","doi-asserted-by":"crossref","first-page":"3970","DOI":"10.1093\/nar\/27.20.3970","article-title":"Genetic organization of \u03b1-bungarotoxins from Bungarus multicinctus (Taiwan banded krait): evidence showing that the production of \u03b1-bungarotoxin isotoxins is not derived from edited mRNAs","volume":"27","author":"Chang","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0235","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s00239-003-2461-2","article-title":"Molecular evolution and phylogeny of elapid snake venom three-finger toxins","volume":"57","author":"Fry","year":"2003","journal-title":"J. Mol. Evol."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0240","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.3892\/ol.2014.2467","article-title":"Antitumor activity of cobrotoxin in human lung adenocarcinoma A549 cells and following transplantation in nude mice","volume":"8","author":"Shen","year":"2014","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0245","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0020695","article-title":"Inhibition of the nicotinic acetylcholine receptors by cobra venom \u03b1-neurotoxins: is there a perspective in lung cancer treatment?","volume":"6","author":"Alama","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.ijbiomac.2020.08.163_bb0250","doi-asserted-by":"crossref","DOI":"10.1038\/srep28660","article-title":"Phosphocholine-an agonist of metabotropic but not of ionotropic functions of \u03b19-containing nicotinic acetylcholine receptors","volume":"6","author":"Richter","year":"2016","journal-title":"Sci. Rep."}],"container-title":["International Journal of Biological Macromolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0141813020342549?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0141813020342549?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:04:53Z","timestamp":1788296693000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0141813020342549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":50,"alternative-id":["S0141813020342549"],"URL":"https:\/\/doi.org\/10.1016\/j.ijbiomac.2020.08.163","relation":{},"ISSN":["0141-8130"],"issn-type":[{"value":"0141-8130","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Blocking of negative charged carboxyl groups converts Naja atra neurotoxin to cardiotoxin-like protein","name":"articletitle","label":"Article Title"},{"value":"International Journal of Biological Macromolecules","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ijbiomac.2020.08.163","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}