ArticleThe Journal of biological chemistry2011
Alboserpin, a factor Xa inhibitor from the mosquito vector of yellow fever, binds heparin and membrane phospholipids and exhibits antithrombotic activity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
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- A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes.Insect biochemistry and molecular biology · 2022Article
- Alboserpin, the Main Salivary Anticoagulant from the Disease VectorImmunoHorizons · 2022Article
- Novel salivary antihemostatic activities of long-form D7 proteins from the malaria vector Anopheles gambiae facilitate hematophagy.The Journal of biological chemistry · 2022Article
- Integrated analysis of the sialotranscriptome and sialoproteome of the rat flea Xenopsylla cheopis.Journal of proteomics · 2022Article
- Multiple Salivary Proteins fromViruses · 2022Article
- Biochemical characterization of AeD7L2 and its physiological relevance in blood feeding in the dengue mosquito vector, Aedes aegypti.The FEBS journal · 2021Article
- Comprehensive Quantitative Proteome Analysis ofFrontiers in physiology · 2021Article
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- A deep insight into the male and female sialotranscriptome of adult Culex tarsalis mosquitoes.Insect biochemistry and molecular biology · 2018Article
- Identification and partial characterization of a novel serpin from Eudiplozoon nipponicum (Monogenea, Polyopisthocotylea).Parasite (Paris, France) · 2018Article
- Comparative Evolution of Sand Fly Salivary Protein Families and Implications for Biomarkers of Vector Exposure and Salivary Vaccine Candidates.Frontiers in cellular and infection microbiology · 2018Article
- Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa.Toxins · 2017Article
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland anticoagulant from the mosquito and yellow fever vector Aedes albopictus, has been characterized. cDNA of Alboserpin predicts a 45-kDa protein that belongs to the serpin family of protease inhibitors. Recombinant Alboserpin displays stoichiometric, competitive, reversible and tight binding to FXa (picomolar range). Binding is highly specific and is not detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes. Alboserpin displays high affinity binding to heparin (K(D) ~ 20 nM), but no change in FXa inhibition was observed in the presence of the cofactor, implying that bridging mechanisms did not take place. Notably, Alboserpin was also found to interact with phosphatidylcholine and phosphatidylethanolamine but not with phosphatidylserine. Further, annexin V (in the absence of Ca(2+)) or heparin outcompetes Alboserpin for binding to phospholipid vesicles, suggesting a common binding site. Consistent with its activity, Alboserpin blocks prothrombinase activity and increases both prothrombin time and activated partial thromboplastin time in vitro or ex vivo. Furthermore, Alboserpin prevents thrombus formation provoked by ferric chloride injury of the carotid artery and increases bleeding in a dose-dependent manner. Alboserpin emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity. It conceivably uses heparin and phosphatidylcholine/phosphatidylethanolamine as anchors to increase protein localization and effective concentration at sites of injury, cell activation, or inflammation.
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