{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:09:26Z","timestamp":1770815366216,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T00:00:00Z","timestamp":1547078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["DP150103990"],"award-info":[{"award-number":["DP150103990"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Snake venom neurotoxins are potent antagonists of nicotinic acetylcholine receptors (nAChRs). Here, we describe a novel member of class 3c long\u2010chain neurotoxin drysdalin from the venom of\n                    <jats:italic>Drysdalia coronoides<\/jats:italic>\n                    . Drysdalin lacks three of the eight conserved classical functional residues critical for nAChRs interaction. Despite such a drastic alteration of the functional site, recombinant drysdalin showed irreversible postsynaptic neurotoxicity with nanomolar potency and selectively antagonizes the rodent muscle (\u03b11)\n                    <jats:sub>2<\/jats:sub>\n                    \u03b21\u03b4\u03b5, and human \u03b17 and \u03b19\u03b110 nAChRs, but had no significant activity at the human \u03b13\u03b22, \u03b13\u03b24, \u03b14\u03b22, and \u03b14\u03b24 nAChRs. Substitution of Leu34 and Ala37 residues with the conserved Arg had minimal impact on the potency whereas conserved Phe replacement of residue Arg30 substantially reduced or abolished inhibitory activity. In contrast, truncation of the 24\u2010residue long C\u2010terminal tail leads to complete loss in (a) activity at \u03b19\u03b110 nAChR; and (b) irreversibility with reduced potency at the muscle and \u03b17 nAChRs. Overall, the non\u2010conserved Arg30 residue together with the uniquely long C\u2010terminal tail contribute to the inhibitory activity of drysdalin at the nAChRs suggesting, at least for drysdalin, functional rather than sequence conservation plays a critical role in determining the activity of the toxin.\n                  <\/jats:p>","DOI":"10.1096\/fba.1027","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T11:00:55Z","timestamp":1553511655000},"page":"115-131","source":"Crossref","is-referenced-by-count":15,"title":["Drysdalin, an antagonist of nicotinic acetylcholine receptors highlights the importance of functional rather than structural conservation of amino acid residues"],"prefix":"10.1096","volume":"1","author":[{"given":"Ritu","family":"Chandna","sequence":"first","affiliation":[{"name":"Protein Science Laboratory, Department of Biological Sciences National University of Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han\u2010Shen","family":"Tae","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong Wollongong NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria A. L.","family":"Seymour","sequence":"additional","affiliation":[{"name":"Burnet Institute Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shifali","family":"Chathrath","sequence":"additional","affiliation":[{"name":"Protein Science Laboratory, Department of Biological Sciences National University of Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong Wollongong NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Manjunatha","family":"Kini","sequence":"additional","affiliation":[{"name":"Protein Science Laboratory, Department of Biological Sciences National University of Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05935.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj070486"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.108.000562"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003269"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.08.012"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-005-3968-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2002.03725.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2013.01.019"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00327a036"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.5b00492"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(87)90002-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm040219e"},{"key":"e_1_2_8_15_1","first-page":"109","article-title":"Three\u2010finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: pharmacological tools and endogenous modulators","volume":"36","author":"Tsetlin VI","journal-title":"Pharmacol Sci"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909746199"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.49.34851"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.16.9362"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi990045g"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.10.004"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.06.024"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr1008916"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1960.tb01264.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-185257-3.50017-3"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/md15060170"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2014.11.003"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(01)00087-3"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.286.6366.678"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.074161"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12154-009-0029-3"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600620"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205483200"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1942"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20130636"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20130638"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-8-91"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.6.1504S"}],"container-title":["FASEB BioAdvances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffba.1027","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fba.1027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T19:29:18Z","timestamp":1761679758000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fba.1027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,10]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1096\/fba.1027"],"URL":"https:\/\/doi.org\/10.1096\/fba.1027","archive":["Portico"],"relation":{},"ISSN":["2573-9832","2573-9832"],"issn-type":[{"value":"2573-9832","type":"print"},{"value":"2573-9832","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,10]]}}}