ArticleBiochemistry2006
Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: the N-terminal region is more important than enzymatic activity.
Article in Biochemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- A Pseudoenzymatic Regulatory Role of the Noncatalytic Subunit of the Neurotoxin Vipoxin at Arachidonic-Acid-Containing Membrane Interfaces.Membranes · 2026Article
- Crystal structure and functional characterization of an Asp49 phospholipase AActa crystallographica. Section F, Structural biology communications · 2026Article
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- Precise mapping of a snake venom phospholipase AToxicon : official journal of the International Society on Toxinology · 2025Article
- An in-depth exploration of snake venom-derived molecules for drug discovery in advancing antiviral therapeutics.Heliyon · 2024Review
- 3-NAntC: A Potent Crotoxin B-Derived Peptide against the Triple-Negative MDA-MB-231 Breast Cancer Cell Line.Molecules (Basel, Switzerland) · 2024Article
- Article
- One Size Fits All-Venomics of the Iberian Adder (Toxins · 2023Article
- Catalytically Active Snake Venom PLAJournal of medicinal chemistry · 2023Review
- High-throughput proteomics and in vitro functional characterization of the 26 medically most important elapids and vipers from sub-Saharan Africa.GigaScience · 2022Article
- What do secreted phospholipases ABiochimie · 2021Review
- Chicken antibodies against venom proteins ofThe journal of venomous animals and toxins including tropical diseases · 2020Article
- Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase.Biochemical Society transactions · 2020Review
- High throughput screening and identification of coagulopathic snake venom proteins and peptides using nanofractionation and proteomics approaches.PLoS neglected tropical diseases · 2020Article
- Activity of two key toxin groups in Australian elapid venoms show a strong correlation to phylogeny but not to diet.BMC evolutionary biology · 2020Article
- Antimalarial Activity of Human Group IIA Secreted Phospholipase AInfection and immunity · 2019Article
- The neurotoxic secreted phospholipase AScientific reports · 2019Article
- Variations in neurotoxicity and proteome profile of Malayan krait (Bungarus candidus) venoms.PloS one · 2019Article
- Parasitoid Jewel Wasp Mounts Multipronged Neurochemical Attack to Hijack a Host Brain.Molecular & cellular proteomics : MCP · 2019Article
- Article
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Authors and funding
16 authors.
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Abstract
Several snake venom secreted phospholipases A2 (sPLA2s) including OS2 exert a variety of pharmacological effects ranging from central neurotoxicity to anti-HIV activity by mechanisms that are not yet fully understood. To conclusively address the role of enzymatic activity and map the key structural elements of OS2 responsible for its pharmacological properties, we have prepared single point OS2 mutants at the catalytic site and large chimeras between OS2 and OS1, a homologous but nontoxic sPLA2. Most importantly, we found that the enzymatic activity of the active site mutant H48Q is 500-fold lower than that of the wild-type protein, while central neurotoxicity is only 16-fold lower, providing convincing evidence that catalytic activity is at most a minor factor that determines central neurotoxicity. The chimera approach has identified the N-terminal region (residues 1-22) of OS2, but not the central one (residues 58-89), as crucial for both enzymatic activity and pharmacological effects. The C-terminal region of OS2 (residues 102-119) was found to be critical for enzymatic activity, but not for central neurotoxicity and anti-HIV activity, allowing us to further dissociate enzymatic activity and pharmacological effects. Finally, direct binding studies with the C-terminal chimera, which poorly binds to phospholipids while it is still neurotoxic, led to the identification of a subset of brain N-type receptors which may be directly involved in central neurotoxicity.
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