{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T13:25:52Z","timestamp":1773581152793,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,12,12]],"date-time":"2003-12-12T00:00:00Z","timestamp":1071187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Scorpion \u03b1\u2010K<jats:sup>+<\/jats:sup> channel toxins are a large family of polypeptides with a similar structure but diverse pharmacological activities. Despite many structural and functional data available at present, little progress has been made in understanding the toxin\u2032s molecular basis responsible for the functional diversification. In this paper, we report the first complete cDNA sequences of toxins belonging to subfamily 6 and identify five new members, called \u03b1\u2010KTx 6.6\u20106.10. By analyzing the rates of mutations that occurred in the corresponding cDNAs, we suggest that accelerated evolution in toxin\u2010coding regions may be associated with the functional diversification of this subfamily. To pinpoint sites probably involved in the functional diversity of \u03b1\u2010KTx family, we analyzed this family of sequences using the evolutionary trace method. This analysis highlighted one channel\u2010binding surface common for all the members. This surface is composed of one conserved lysine residue at position <jats:italic>29<\/jats:italic> assisted by other residues at positions <jats:italic>10<\/jats:italic>, <jats:italic>26<\/jats:italic>, <jats:italic>27<\/jats:italic>, <jats:italic>32<\/jats:italic>, <jats:italic>34<\/jats:italic>, and <jats:italic>36<\/jats:italic>. Of them, the positions <jats:italic>29<\/jats:italic>, <jats:italic>32<\/jats:italic>, and 34 have been reported to be the most major determinants of channel specificity. Interestingly, another contrary surface was also observed at a higher evolutionary time cut\u2010off value, which may be involved in the binding of ERG (ether\u2010a\u2010go\u2010go\u2010related gene) channel\u2010specific toxins. The good match between the trace residues and the functional epitopes of the toxins suggested that the evolutionary trace results reported here can be applied to predict channel\u2010binding sites of the toxins. Because, the side\u2010chain variation in the trace positions is strongly linked with the functional alteration and channel\u2010binding surface transfer of \u03b1\u2010KTx family, we conclude that our findings should also be important for the rational design of new toxins targeting a given potassium channel with high selectivity. Proteins 2004;54:000\u2013000. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.10588","type":"journal-article","created":{"date-parts":[[2003,12,23]],"date-time":"2003-12-23T12:12:55Z","timestamp":1072181575000},"page":"361-370","source":"Crossref","is-referenced-by-count":33,"title":["Evolutionary trace analysis of scorpion toxins specific for K\u2010channels"],"prefix":"10.1002","volume":"54","author":[{"given":"Shunyi","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Huys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Dyason","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fons","family":"Verdonck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Tytgat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,12,12]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1017062613503"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(98)00157-3"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5360.106"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(99)01398-X"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-9639(02)00458-2"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1720574"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(01)00120-9"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716527"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.49.31013"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.7.4302"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111258200"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.5.2639"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204083200"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)75251-X"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(00)00214-2"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.2.1201"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5360.69"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81018-1"},{"key":"e_1_2_6_20_2","first-page":"548","article-title":"Protein: structure, function and evolution","author":"Clote P","year":"2002","journal-title":"Pacific Symposium on BioComputing"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(02)00284-1"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.23.8998"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(98)01285-7"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a026236"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/13.12.839"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0167"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(00)00081-7"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.8.12.2672"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0134(199711)29:3<321::AID-PROT6>3.0.CO;2-D"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi991685m"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6603(08)61036-3"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511623486"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03256-8"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00168a008"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560040805"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80057-4"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006827200"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3011.1999.00107.x"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005973200"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3280321"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(98)00153-6"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.18.13605"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02433-9"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006810200"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0571hyp"}],"container-title":["Proteins: Structure, Function, and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprot.10588","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prot.10588","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T09:50:36Z","timestamp":1697190636000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.10588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,12,12]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,2]]}},"alternative-id":["10.1002\/prot.10588"],"URL":"https:\/\/doi.org\/10.1002\/prot.10588","archive":["Portico"],"relation":{},"ISSN":["0887-3585","1097-0134"],"issn-type":[{"value":"0887-3585","type":"print"},{"value":"1097-0134","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,12,12]]}}}