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Open AccessArticle

Aspartic Acid Isomerization Characterized by High Definition Mass Spectrometry Significantly Alters the Bioactivity of a Novel Toxin from Poecilotheria

1
Carbon Dynamics Institute LLC, Sherman, IL 62684, USA
2
Chemistry Department, University of Illinois Springfield, Springfield, IL 62703, USA
3
College of Liberal Arts & Sciences, University of Illinois Springfield, Springfield, IL 62703, USA
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(4), 207; https://doi.org/10.3390/toxins12040207
Received: 2 March 2020 / Revised: 20 March 2020 / Accepted: 23 March 2020 / Published: 25 March 2020
(This article belongs to the Special Issue Proteomics Analysis in Animal Venom)
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 “tiger” 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’s diminished physiological effects. This study establishes the value of a HDMSE approach to toxin screening and characterization. View Full-Text
Keywords: Voltage-gated sodium channel; venom; Poecilotheria; poecilotheriatoxin; deamidation; isomerization; high definition mass spectrometry; ion mobility; supplemental activation Voltage-gated sodium channel; venom; Poecilotheria; poecilotheriatoxin; deamidation; isomerization; high definition mass spectrometry; ion mobility; supplemental activation
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MDPI and ACS Style

Johnson, S.R.; Rikli, H.G. Aspartic Acid Isomerization Characterized by High Definition Mass Spectrometry Significantly Alters the Bioactivity of a Novel Toxin from Poecilotheria. Toxins 2020, 12, 207.

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