Venom gland transcriptomics and bioactivity profiling suggest bifunctional hyaluronidase activity in the venom of Mesobuthus crucittii (Scorpiones: Buthidae)
Abstract
Introduction:
Scorpion venom is a rich source of bioactive molecules with promising biomedical applications. Hyaluronidases are venom-associated enzymes that facilitate toxin diffusion by degrading extracellular matrix glycosaminoglycans, yet their structural diversity and substrate specificity in scorpion venoms remain insufficiently explored. This study aimed to identify and characterize a novel hyaluronidase from the venom gland of the Iranian endemic scorpion Mesobuthus crucittii and evaluate its biochemical and structural properties.
Methods:
Venom gland transcriptome profiling was performed. Hyaluronidase sequences were analyzed in silico via phylogenetic reconstruction, motif prediction, physicochemical property calculation, and structural modeling. Molecular docking was conducted to explore interactions with hyaluronic acid and chondroitin sulfate substrates. Enzymatic activity and thermal stability were experimentally evaluated using turbidimetric assays.
Results:
Transcriptomic analysis revealed a diverse toxin repertoire dominated by ion channel modulators and enzymatic components, including a novel precursor encoding a putative hyaluronidase exhibiting a unique cysteine framework with six disulfide bonds and three conserved diagnostic motifs (GDWW, FPDC, and GWGS). Structural modeling suggested catalytic and binding domains consistent with glycosyl hydrolase family 56 enzymes. Molecular docking supported preferential binding affinity toward hyaluronic acid tetrasaccharides rather than longer or highly sulfated glycosaminoglycans. Functional assays on crude venom confirmed strong hyaluronan degradation and slower chondroitin sulfate hydrolysis, indicating dual substrate activity.
Discussion:
This study supports the existence of a structurally distinct scorpion venom hyaluronidase with putative bifunctional substrate activity. These findings expand current understanding of scorpion venom enzyme evolution and highlight the enzyme's translational potential.
Baradaran, M., Salabi, F., Payab, N., Kazemi, S. M., Santibáñez-López, C. E., & Lüddecke, T. (2026). Venom gland transcriptomics and bioactivity profiling suggest bifunctional hyaluronidase activity in the venom of Mesobuthus crucittii (Scorpiones: Buthidae). Frontiers in Molecular Biosciences, 13, 1807239. https://doi.org/10.3389/fmolb.2026.1807239 (DOI is still not registered).
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Frontiers in Molecular Biosciences
