{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:44:12Z","timestamp":1792374252868,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T00:00:00Z","timestamp":1539129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31600669"],"award-info":[{"award-number":["31600669"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","award":["2018JJ3339"],"award-info":[{"award-number":["2018JJ3339"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Exploring the interaction of ligands with voltage-gated sodium channels (NaVs) has advanced our understanding of their pharmacology. Herein, we report the purification and characterization of a novel non-selective mammalian and bacterial NaVs toxin, JZTx-14, from the venom of the spider Chilobrachys jingzhao. This toxin potently inhibited the peak currents of mammalian NaV1.2\u20131.8 channels and the bacterial NaChBac channel with low IC50 values (&lt;1 \u00b5M), and it mainly inhibited the fast inactivation of the NaV1.9 channel. Analysis of NaV1.5\/NaV1.9 chimeric channel showed that the NaV1.5 domain II S3\u20134 loop is involved in toxin association. Kinetics data obtained from studying toxin\u2013NaV1.2 channel interaction showed that JZTx-14 was a gating modifier that possibly trapped the channel in resting state; however, it differed from site 4 toxin HNTx-III by irreversibly blocking NaV currents and showing state-independent binding with the channel. JZTx-14 might stably bind to a conserved toxin pocket deep within the NaV1.2\u20131.8 domain II voltage sensor regardless of channel conformation change, and its effect on NaVs requires the toxin to trap the S3\u20134 loop in its resting state. For the NaChBac channel, JZTx-14 positively shifted its conductance-voltage (G\u2013V) and steady-state inactivation relationships. An alanine scan analysis of the NaChBac S3\u20134 loop revealed that the 108th phenylalanine (F108) was the key residue determining the JZTx-14\u2013NaChBac interaction. In summary, this study provided JZTx-14 with potent but promiscuous inhibitory activity on both the ancestor bacterial NaVs and the highly evolved descendant mammalian NaVs, and it is a useful probe to understand the pharmacology of NaVs.<\/jats:p>","DOI":"10.3390\/toxins10100408","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T11:53:13Z","timestamp":1539172393000},"page":"408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Purification and Characterization of JZTx-14, a Potent Antagonist of Mammalian and Prokaryotic Voltage-Gated Sodium Channels"],"prefix":"10.3390","volume":"10","author":[{"given":"Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfang","family":"Tang","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangyu","family":"Liu","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoliang","family":"Hu","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songping","family":"Liang","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5848-2458","authenticated-orcid":false,"given":"Cheng","family":"Tang","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Liu","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1749-6632.1999.tb11272.x","article-title":"Diversity of mammalian voltage-gated sodium channels","volume":"868","author":"Goldin","year":"1999","journal-title":"Ann. 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