{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:30:56Z","timestamp":1791307856186,"version":"4.3.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T00:00:00Z","timestamp":1395964800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"},{"start":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T00:00:00Z","timestamp":1395964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/srep04509","type":"journal-article","created":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T10:22:45Z","timestamp":1396002165000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases"],"prefix":"10.1038","volume":"4","author":[{"given":"M. Harunur","family":"Rashid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Redwan","family":"Huq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Tanner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Chhabra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith K.","family":"Khoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosendo","family":"Estrada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Dhawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satendra","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Pennington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Beeton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Kuyucak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond S.","family":"Norton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,3,28]]},"reference":[{"key":"BFsrep04509_CR1","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1172\/JCI16921","volume":"111","author":"H Wulff","year":"2003","unstructured":"Wulff, H. et al. The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. J Clin Invest 111, 1703\u20131713 (2003).","journal-title":"J Clin Invest"},{"key":"BFsrep04509_CR2","doi-asserted-by":"publisher","first-page":"17414","DOI":"10.1073\/pnas.0605136103","volume":"103","author":"C Beeton","year":"2006","unstructured":"Beeton, C. et al. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci U S A 103, 17414\u201317419 (2006).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep04509_CR3","doi-asserted-by":"publisher","first-page":"313","DOI":"10.2174\/187152811797200641","volume":"10","author":"C Beeton","year":"2011","unstructured":"Beeton, C., Pennington, M. W. & Norton, R. S. Analogs of the sea anemone potassium channel blocker ShK for the treatment of autoimmune diseases. Inflamm Allergy Drug Targets 10, 313\u2013321 (2011).","journal-title":"Inflamm Allergy Drug Targets"},{"key":"BFsrep04509_CR4","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.toxicon.2011.07.016","volume":"59","author":"V Chi","year":"2012","unstructured":"Chi, V. et al. Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases. Toxicon 59, 529\u2013546 (2012).","journal-title":"Toxicon"},{"key":"BFsrep04509_CR5","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1042\/bj3280321","volume":"328 (Pt1)","author":"B Lebrun","year":"1997","unstructured":"Lebrun, B. et al. A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom. Biochem J 328 (Pt1), 321\u2013327 (1997).","journal-title":"Biochem J"},{"key":"BFsrep04509_CR6","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1110\/ps.8.12.2672","volume":"8","author":"P Savarin","year":"1999","unstructured":"Savarin, P. et al. Structural and functional consequences of the presence of a fourth disulfide bridge in the scorpion short toxins: solution structure of the potassium channel inhibitor HsTX1. Protein Sci 8, 2672\u20132685 (1999).","journal-title":"Protein Sci"},{"key":"BFsrep04509_CR7","doi-asserted-by":"publisher","first-page":"55690","DOI":"10.1074\/jbc.M410055200","volume":"279","author":"I Regaya","year":"2004","unstructured":"Regaya, I. et al. Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins. J Biol Chem 279, 55690\u201355696 (2004).","journal-title":"J Biol Chem"},{"key":"BFsrep04509_CR8","doi-asserted-by":"publisher","first-page":"3996","DOI":"10.1016\/j.febslet.2012.09.038","volume":"586","author":"MW Pennington","year":"2012","unstructured":"Pennington, M. W. et al. A C-terminally amidated analogue of ShK is a potent and selective blocker of the voltage-gated potassium channel Kv1.3. FEBS Lett 586, 3996\u20134001 (2012).","journal-title":"FEBS Lett"},{"key":"BFsrep04509_CR9","doi-asserted-by":"publisher","first-page":"e78712","DOI":"10.1371\/journal.pone.0078712","volume":"8","author":"MH Rashid","year":"2013","unstructured":"Rashid, M. H. et al. A potent and selective peptide blocker of the Kv1.3 channel: prediction from free-energy simulations and experimental confirmation. PloS one 8, e78712 (2013).","journal-title":"PloS one"},{"key":"BFsrep04509_CR10","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1124\/mol.108.052704","volume":"75","author":"MW Pennington","year":"2009","unstructured":"Pennington, M. W. et al. Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes. Mol Pharmacol 75, 762\u2013773 (2009).","journal-title":"Mol Pharmacol"},{"key":"BFsrep04509_CR11","unstructured":"Norton, R. S., Pennington, M. W. & Beeton, C. [Transforming a toxin into a therapeutic: the sea anemone potassium channel blocker ShK toxin for treatment of autoimmune diseases]. Venoms to drugs: Venom as a source for the development of human therapeutics [King G. F. (ed.)] [in press] (Royal Society of Chemistry, London, 2014)."},{"key":"BFsrep04509_CR12","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1021\/jp410950h","volume":"118","author":"MH Rashid","year":"2014","unstructured":"Rashid, M. H. & Kuyucak, S. Free energy simulations of binding of HsTx1 toxin to Kv1 potassium channels: the basis of Kv1.3\/Kv1.1 selectivity. J Phys Chem B 118, 707\u2013716 (2014).","journal-title":"J Phys Chem B"},{"key":"BFsrep04509_CR13","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1016\/j.bpj.2011.03.052","volume":"100","author":"PC Chen","year":"2011","unstructured":"Chen, P. C. & Kuyucak, S. Accurate determination of the binding free energy for KcsA-charybdotoxin complex from the potential of mean force calculations with restraints. Biophys J 100, 2466\u20132474 (2011).","journal-title":"Biophys J"},{"key":"BFsrep04509_CR14","doi-asserted-by":"publisher","first-page":"4812","DOI":"10.1021\/jp300639x","volume":"116","author":"MH Rashid","year":"2012","unstructured":"Rashid, M. H. & Kuyucak, S. Affinity and selectivity of ShK toxin for the Kv1 potassium channels from free energy simulations. J Phys Chem B 116, 4812\u20134822 (2012).","journal-title":"J Phys Chem B"},{"key":"BFsrep04509_CR15","doi-asserted-by":"publisher","first-page":"16407","DOI":"10.1021\/bi962463g","volume":"35","author":"MW Pennington","year":"1996","unstructured":"Pennington, M. W. et al. An essential binding surface for ShK toxin interaction with rat brain potassium channels. Biochemistry 35, 16407\u201316411 (1996).","journal-title":"Biochemistry"},{"key":"BFsrep04509_CR16","doi-asserted-by":"publisher","first-page":"e76740","DOI":"10.1371\/journal.pone.0076740","volume":"8","author":"S Koshy","year":"2013","unstructured":"Koshy, S. et al. Blocking KCa3.1 channels increases tumor cell killing by a subpopulation of human natural killer lymphocytes. PloS one 8, e76740 (2013).","journal-title":"PloS one"},{"key":"BFsrep04509_CR17","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/cbdd.12055","volume":"81","author":"DJ Craik","year":"2013","unstructured":"Craik, D. J., Fairlie, D. P., Liras, S. & Price, D. The future of peptide-based drugs. Chem Biol Drug Des 81, 136\u2013147 (2013).","journal-title":"Chem Biol Drug Des"},{"key":"BFsrep04509_CR18","doi-asserted-by":"publisher","first-page":"19058","DOI":"10.1074\/jbc.M802054200","volume":"283","author":"S Han","year":"2008","unstructured":"Han, S. et al. Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease. J Biol Chem 283, 19058\u201319065 (2008).","journal-title":"J Biol Chem"},{"key":"BFsrep04509_CR19","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1124\/pr.55.4.9","volume":"55","author":"GA Gutman","year":"2003","unstructured":"Gutman, G. A. et al. International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels. Pharmacol Rev 55, 583\u2013586 (2003).","journal-title":"Pharmacol Rev"},{"key":"BFsrep04509_CR20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","author":"W Humphrey","year":"1996","unstructured":"Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J Mol Graph 14, 33\u201338 (1996).","journal-title":"J Mol Graph"},{"key":"BFsrep04509_CR21","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1021\/ja026939x","volume":"125","author":"C Dominguez","year":"2003","unstructured":"Dominguez, C., Boelens, R. & Bonvin, A. M. HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. J Am Chem Soc 125, 1731\u20131737 (2003).","journal-title":"J Am Chem Soc"},{"key":"BFsrep04509_CR22","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1002\/jcc.20289","volume":"26","author":"JC Phillips","year":"2005","unstructured":"Phillips, J. C. et al. Scalable molecular dynamics with NAMD. J Comput Chem 26, 1781\u20131802 (2005).","journal-title":"J Comput Chem"},{"key":"BFsrep04509_CR23","doi-asserted-by":"publisher","first-page":"7830","DOI":"10.1021\/jp101759q","volume":"114","author":"JB Klauda","year":"2010","unstructured":"Klauda, J. B. et al. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114, 7830\u20137843 (2010).","journal-title":"J Phys Chem B"},{"key":"BFsrep04509_CR24","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1002\/jcc.540130812","volume":"13","author":"S Kumar","year":"1992","unstructured":"Kumar, S., Bouzida, D., Swensen, R. H., Kollman, P. A. & Rosenberg, J. M. The weighted histogram analysis method for free-energy calculations on biomolecules. J Comput Chem 13, 1011\u20131021 (1992).","journal-title":"J Comput Chem"},{"key":"BFsrep04509_CR25","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/S0026-895X(25)10594-4","volume":"45","author":"S Grissmer","year":"1994","unstructured":"Grissmer, S. et al. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5 and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol 45, 1227\u20131234 (1994).","journal-title":"Mol Pharmacol"},{"key":"BFsrep04509_CR26","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/10567","volume":"5","author":"A Flugel","year":"1999","unstructured":"Flugel, A., Willem, M., Berkowicz, T. & Wekerle, H. Gene transfer into CD4+ T lymphocytes: green fluorescent protein-engineered, encephalitogenic T cells illuminate brain autoimmune responses. Nat Med 5, 843\u2013847 (1999).","journal-title":"Nat Med"},{"key":"BFsrep04509_CR27","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.immuni.2008.07.015","volume":"29","author":"MP Matheu","year":"2008","unstructured":"Matheu, M. P. et al. Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block. Immunity 29, 602\u2013614 (2008).","journal-title":"Immunity"},{"key":"BFsrep04509_CR28","first-page":"402","volume":"10","author":"C Beeton","year":"2007","unstructured":"Beeton, C. & Chandy, K. G. Preparing T cell growth factor from rat splenocytes. J Vis Exp 10, 402 (2007).","journal-title":"J Vis Exp"},{"key":"BFsrep04509_CR29","first-page":"326","volume":"8","author":"C Beeton","year":"2007","unstructured":"Beeton, C. & Chandy, K. G. Enrichment of NK cells from human blood with the RosetteSep kit from StemCell technologies. J Vis Exp 8, 326 (2007).","journal-title":"J Vis Exp"},{"key":"BFsrep04509_CR30","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.toxicon.2012.05.017","volume":"60","author":"SC Chang","year":"2012","unstructured":"Chang, S. C. et al. Expression and isotopic labelling of the potassium channel blocker ShK toxin as a thioredoxin fusion protein in bacteria. Toxicon 60, 840\u2013850 (2012).","journal-title":"Toxicon"},{"key":"BFsrep04509_CR31","first-page":"e50166","volume":"73","author":"BC Evans","year":"2013","unstructured":"Evans, B. C. et al. Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. J Vis Exp 73, e50166 (2013).","journal-title":"J Vis Exp"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep04509.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep04509","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep04509.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T05:44:20Z","timestamp":1746164660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep04509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,28]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,12,17]]}},"alternative-id":["BFsrep04509"],"URL":"https:\/\/doi.org\/10.1038\/srep04509","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,28]]},"assertion":[{"value":"24 December 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4509"}}