{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:53:00Z","timestamp":1783061580647,"version":"3.54.6"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T00:00:00Z","timestamp":1626566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM103640-08"],"award-info":[{"award-number":["P20GM103640-08"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21NS109896"],"award-info":[{"award-number":["R21NS109896"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS053422"],"award-info":[{"award-number":["R01NS053422"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The voltage-gated sodium channel Nav1.8 is linked to neuropathic and inflammatory pain, highlighting the potential to serve as a drug target. However, the biophysical mechanisms that regulate Nav1.8 activation and inactivation gating are not completely understood. Progress has been hindered by a lack of biochemical tools for examining Nav1.8 gating mechanisms. Arizona bark scorpion (Centruroides sculpturatus) venom proteins inhibit Nav1.8 and block pain in grasshopper mice (Onychomys torridus). These proteins provide tools for examining Nav1.8 structure\u2013activity relationships. To identify proteins that inhibit Nav1.8 activity, venom samples were fractioned using liquid chromatography (reversed-phase and ion exchange). A recombinant Nav1.8 clone expressed in ND7\/23 cells was used to identify subfractions that inhibited Nav1.8 Na+ current. Mass-spectrometry-based bottom-up proteomic analyses identified unique peptides from inhibitory subfractions. A search of the peptides against the AZ bark scorpion venom gland transcriptome revealed four novel proteins between 40 and 60% conserved with venom proteins from scorpions in four genera (Centruroides, Parabuthus, Androctonus, and Tityus). Ranging from 63 to 82 amino acids, each primary structure includes eight cysteines and a \u201cCXCE\u201d motif, where X = an aromatic residue (tryptophan, tyrosine, or phenylalanine). Electrophysiology data demonstrated that the inhibitory effects of bioactive subfractions can be removed by hyperpolarizing the channels, suggesting that proteins may function as gating modifiers as opposed to pore blockers.<\/jats:p>","DOI":"10.3390\/toxins13070501","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T21:18:52Z","timestamp":1626643132000},"page":"501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification and Characterization of Novel Proteins from Arizona Bark Scorpion Venom That Inhibit Nav1.8, a Voltage-Gated Sodium Channel Regulator of Pain Signaling"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-9673","authenticated-orcid":false,"given":"Tarek Mohamed","family":"Abd El-Aziz","sequence":"first","affiliation":[{"name":"Department of Cellular & Integrative Physiology, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA"},{"name":"Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7264-7637","authenticated-orcid":false,"given":"Jake","family":"Kline","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK 73019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Gridley","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK 73019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyse","family":"Heaston","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK 73019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus D.","family":"Linse","sequence":"additional","affiliation":[{"name":"Bio-Synthesis Inc., 612 E. Main Street, Lewisville, TX 75057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-8615","authenticated-orcid":false,"given":"Micaiah J.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida State University, 319 Stadium Drive, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0356-2178","authenticated-orcid":false,"given":"Darin R.","family":"Rokyta","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida State University, 319 Stadium Drive, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Stockand","sequence":"additional","affiliation":[{"name":"Department of Cellular & Integrative Physiology, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore R.","family":"Cummins","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-1046","authenticated-orcid":false,"given":"Luca","family":"Fornelli","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK 73019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee H.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK 73019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and Molecular Mechanisms of Pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9075","DOI":"10.1073\/pnas.0901507106","article-title":"Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli","volume":"106","author":"Cavanaugh","year":"2009","journal-title":"Proc. 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