Lys49 myotoxins, secreted phospholipase A2-like proteins of viperid venoms: A comprehensive review

Lomonte, Bruno

doi:10.1016/j.toxicon.2023.107024

Cited by 22 publications

(17 citation statements)

References 313 publications

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“…This is in line with previous studies focusing on the membrane-disrupting effect of PLA 2 s in snake venoms. These toxins disrupt the membrane by hydrolysis of the phospholipids (in the case of enzymatically active toxins), whereas the enzymatically inactive PLA 2 homologs exert their effects via perturbation of the plasma membrane ( Montecucco et al, 2008 ; Lomonte, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation

Bittenbinder,

Wachtel,

Pereira

et al. 2024

Toxicon: X

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Section: Resultsmentioning

confidence: 99%

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation

Bittenbinder,

Wachtel,

Pereira

et al. 2024

Toxicon: X

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“…The presence of aspartic acid at this position (D49) imparts the catalytic activity critical for PLA 2 enzymatic reaction [ 70 ], and it is highly conserved across lineages, including D. acutus (Q1ZY03), T. stejnegeri (Q6H3C7), T. puniceus (Q2YHJ7), and Gloydius brevicaudus (A0A0H3U1W0) of the Old World, as well as Crotalus atrox (P00624) and Bothrops jararacussu (Q90249) of the New World ( Figure 5 ). The substitution of this amino acid (D) for lysine (K) in Cr-PLA03 is anticipated to result in a complete loss of phospholipase activity while gaining myotoxic activity, a toxic trait of neofunctionalization [ 71 ]. Clinically, systemic myotoxicity is rarely reported in C. rhodostoma envenoming, although the various PLA 2 enzymes expressed may act in synergism with other toxins, contributing to inflammation, cytolytic, and tissue-destructive effects.…”

Section: Resultsmentioning

confidence: 99%

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan

et al. 2023

Toxins

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In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study de novo assembled and analyzed the venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM, Fragments Per Kilobase Million), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI > PII > PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensin-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%), and others (1.78%). The expressions of SVMP, CTL, and SVSP correlate with hemorrhagic, anti-platelet, and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) acts by inhibiting platelet aggregation. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitors), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (an ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.

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“…The presence of aspartic acid at this position (D49) imparts catalytic activity critical for PLA2 enzymatic reaction [65], and is highly conserved across lineages including D. acutus (Q1ZY03), T. stejnegeri (Q6H3C7), T. puniceus (Q2YHJ7) and Gloydius brevicaudus (A0A0H3U1W0) of the Old World as well as Crotalus atrox (P00624) and Bothrops jararacussu (Q90249) of the New World (Figure 5). The substitution of this amino acid (D) for lysine (K) in Cr-PLA04 is anticipated to result in a complete loss of phospholipase activity while gaining myotoxic activity, a toxic trait of neofunctionalization [66]. Clinically, systemic myotoxicity is rarely reported in C. rhodostoma envenoming, although the various PLA2 expressed may act in synergism with other toxins, contributing to inflammation, cytolytic and tissue destructive effects.…”

Section: Phospholipase A2 (Pla2)mentioning

confidence: 99%

<em>De Novo </em>Venom Gland Transcriptome Assembly and Characterization for <em>Calloselasma rhodostoma</em> (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan¹,

Tan²,

Ng³

et al. 2023

Preprint

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In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study assembled and analyzed the de novo venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI&gt;PII&gt;PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensinogen-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%) and others (1.78%). The expressions of SVMP, CTL and SVSP correlate with hemorrhagic, anti-platelet and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) is platelet-inhibitory. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitor), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.

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Lys49 myotoxins, secreted phospholipase A2-like proteins of viperid venoms: A comprehensive review

Cited by 22 publications

References 313 publications

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

<em>De Novo </em>Venom Gland Transcriptome Assembly and Characterization for <em>Calloselasma rhodostoma</em> (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

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