{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T05:49:43Z","timestamp":1762926583593,"version":"build-2065373602"},"reference-count":93,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Research in toxinology has created a pharmacological paradox. With an estimated 220,000 venomous animals worldwide, the study of peptidyl toxins provides a vast number of effector molecules. However, due to the complexity of the protein-protein interactions, there are fewer than ten venom-derived molecules on the market. Structural characterization and identification of post-translational modifications are essential to develop biological lead structures into pharmaceuticals. Utilizing advancements in mass spectrometry, we have created a high definition approach that fuses conventional high-resolution MS-MS with ion mobility spectrometry (HDMSE) to elucidate these primary structure characteristics. We investigated venom from ten species of \u201ctiger\u201d spider (Genus: Poecilotheria) and discovered they contain isobaric conformers originating from non-enzymatic Asp isomerization. One conformer pair conserved in five of ten species examined, denominated PcaTX-1a and PcaTX-1b, was found to be a 36-residue peptide with a cysteine knot, an amidated C-terminus, and isoAsp33Asp substitution. Although the isomerization of Asp has been implicated in many pathologies, this is the first characterization of Asp isomerization in a toxin and demonstrates the isomerized product\u2019s diminished physiological effects. This study establishes the value of a HDMSE approach to toxin screening and characterization.<\/jats:p>","DOI":"10.3390\/toxins12040207","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T13:39:34Z","timestamp":1585834774000},"page":"207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Aspartic Acid Isomerization Characterized by High Definition Mass Spectrometry Significantly Alters the Bioactivity of a Novel Toxin from Poecilotheria"],"prefix":"10.3390","volume":"12","author":[{"given":"Stephen R.","family":"Johnson","sequence":"first","affiliation":[{"name":"Carbon Dynamics Institute LLC, Sherman, IL 62684, USA"},{"name":"Chemistry Department, University of Illinois Springfield, Springfield, IL 62703, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hillary G.","family":"Rikli","sequence":"additional","affiliation":[{"name":"College of Liberal Arts &amp; Sciences, University of Illinois Springfield, Springfield, IL 62703, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1073\/pnas.77.1.639","article-title":"Covalent labeling of protein components of the sodium channel with a photoactivable derivative of scorpion toxin","volume":"77","author":"Beneski","year":"1980","journal-title":"Proc. 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