Exploration of the antithrombotic effect of a C type lectin purified from Cerastes cerastes venom by protein-protein docking
Journal Title: UNKNOWN - Year 2018, Vol 2, Issue 2
Abstract
Background: Thromboembolic diseases are a major clinical problem due to their high prevalence and their often fatal consequences. In the present study, an anticoagulant galactoside binding C type lectin “Cc-Lec” was purified and characterized. Methods: Cc-Lec was purified by affinity chromatography on a column of Sepharose 4B coupled with D-lactose. Its homogeneity was verified by SDS-PAGE and ESI-MS. Cc-Lec 3D structure modelization was achieved by homology to Convulxin a snake venom C type lectin. Cc-Lec anticoagulant effect was explored in vivo by i.p. administration to mice, in vitro by native PAGE analysis and in silico by protein-protein docking approach. Results: Cc-Lec is a 34 271,59 Da protein, composed of 160 residues of amino acids for each subunit. Its 3D structure is organized into a homodimer cross-linked with a disulfide bridge and composed of three alpha helices and seven beta strands for each monomer. Cc-Lec functional characterization revealed a durable anticoagulant effect in vivo after 6 and 48h of i.p. administration to mice. This anticoagulant effect is mediated by interaction with FXa and FIXa as showed by native PAGE analysis. Moreover, protein-protein docking results reinforced this data and showed that Cc-Lec interacts with coagulation factors X and IX through their -carboxyglutamic domains. The interaction with factors X and IX requires calcium or calcium and magnesium ions respectively. Conclusion: The anticoagulant effect of Cc-Lec makes it a promising pharmacological target for the diagnosis and/or the therapy of the thromboembolic diseases.
Authors and Affiliations
Fatah Cherifi, Samah Saoud, Fatima Laraba-Djebari
Keywords
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- EP ID EP648632
- DOI 10.26415/2572-004X-vol2iss2p226-227
- Views 80
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Exploration of the antithrombotic effect of a C type lectin purified from Cerastes cerastes venom by protein-protein docking
Background: Thromboembolic diseases are a major clinical problem due to their high prevalence and their often fatal consequences. In the present study, an anticoagulant galactoside binding C type lectin “Cc-Lec” was puri...
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