Yong, Mun Yee and Tan, Kae Yi and Tan, Choo Hock (2025) A genus-wide study on venom proteome variation and phospholipase A2 inhibition in Asian lance-headed pit vipers (genus: Trimeresurus). Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology, 288. p. 110077. ISSN 1532-0456, DOI https://doi.org/10.1016/j.cbpc.2024.110077.
Full text not available from this repository.Abstract
High molecular weight proteins are present abundantly in viperid venoms. The amino acid sequence can be highly variable, contributing to the structure and function diversity of snake venom protein. However, this variability remains poorly understood in many species. The study investigated the venom protein variability in a distinct clade of Asian pit vipers (Trimeresurus species complex) through comparative proteomics, applying gel electrophoresis (SDS-PAGE), liquid chromatography-tandem mass spectrometry (LCMS/MS), and bioinformatic approaches. The proteomes revealed a number of conserved protein families, within each are variably expressed protein paralogs that are unrelated to the snake phylogeny and geographic origin. The expression levels of two major enzymes, i.e., snake venom serine proteinase and metalloproteinase, correlate weakly with procoagulant and hemorrhagic activities, implying co-expression of other functionally versatile toxins in the venom. The phospholipase A2 (PLA2) abundance correlates strongly with its enzymatic activity, and a unique phenotype was discovered in two species expressing extremely little PLA2. The commercial mono-specific antivenom effectively neutralized the venoms' procoagulant and hemorrhagic effects but failed to inhibit the PLA2 activities. Instead, the PLA2 activities of all venoms were effectively inhibited by the small molecule inhibitor varespladib, suggesting its potential to be repurposed as a highly potent adjuvant therapeutic in snakebite envenoming.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya (BKS003-2019), National Tsing Hua University (NTHU) (113Q2767E1), Ministry of Education (MOE) Higher Education Sprout Project" in Taiwan |
| Uncontrolled Keywords: | Venom proteome; Venomics; Varespladib |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine Faculty of Medicine > Department of Molecular Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 20 Mar 2025 01:41 |
| Last Modified: | 20 Mar 2025 01:41 |
| URI: | http://eprints.um.edu.my/id/eprint/47216 |
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