Evidence for existence of venom 5′ nucleotidase in multiple forms through inhibition of concanavalin A

Abstract

Pharmacologically active 5' nucleotidase is a ubiquitously distributed enzyme in snake venoms. In this study the effect of concanavalin A (Con-A) on different snake venoms 5' nucleotidase activity is tested in order to know the protein nature which will ultimately help in purification of the enzyme with high yield. Con-A inhibited Naja naja, Naja kauthia, Naja melanoleuca, Naja naja sputatrix, Agistrodon halys blomhoffii, Bothrops asper and Oxyranus scutellas venom 5' nucleotidase activity at different concentrations. This indicates the presence of glycopart in the protein, thus glycoprotein in nature. Vipera russellii, Vipera plaestenae, Agistrodon contratrix, Bitis orientis, Echis carinatus and Trimeresures malabaricus was not inhibited by Con-A, indicating absence of glycopart in the protein. This study for the first time shows existence of 5' nucleotidase in multimeric forms.

Vanillin Analog – Vanillyl Mandelic Acid, a Novel Specific Inhibitor of Snake Venom 5′‐Nucleotidase

“…Numerous studies have used specific inhibitors of enzymes as a biochemical or pharmacological tool to characterize and establish the mechanism of action . On similar lines, we demonstrated the involvement of Naja naja venom 5′NUC in inducing anticoagulant effect by the use of specific inhibitor .…”

“…On similar lines, we demonstrated the involvement of Naja naja venom 5′NUC in inducing anticoagulant effect by the use of specific inhibitor . Further, we had exemplified that the specific inhibitor of snake venom 5′NUC could be used as a pharmacological tool to decipher the role of 5′NUC in envenomation and also use it as a molecular tool for development of new therapeutic agents in the treatment of ophidian accidents . In the earlier studies, we had demonstrated the potential of vanillin analogs to inhibit snake venom 5′NUC, and reported that vanillic acid was potent with selective inhibition .…”

“…The various inhibitors reported till date seem to depend on protein nature and lack in specificity toward venom 5′NUC. It is reported that Con A inhibited Crotalus atrox and N. naja venom 5′NUC activity by specifically interacting with α‐ D ‐glucose and α‐ D ‐mannose residues in glycoprotein and exerted reversible inhibitory effect . It is also reported that citrate and EDTA also inhibit venom 5′NUC activity by metal‐ion‐chelating effect .…”

“…Although it is widely accepted that 5′NUC plays an important role in snake envenomation strategies, apart from its hemostatic functions modulation, its other pharmacological effects are not well characterized . Several studies have used specific inhibitors of enzymes as a biochemical or pharmacological tool to characterize/or establish its mechanism of action . The involvement of N. naja venom 5′NUC in inducing anticoagulant effect was demonstrated by the use of specific inhibitor, vanillyl acid (VA) .…”

Plant-Derived Toxin Inhibitors as Potential Candidates to Complement Antivenom Treatment in Snakebite Envenomations

“…NUCs have as their main function the generation of adenosine through catalytic activity, which contributes to the immobilization of prey while increasing vascular permeability, and also promotes hypotension, bradycardia and decreased locomotor activity. Among the nucleases, PDE exonucleases catalyze the hydrolysis of phosphodiester bonds, and are recognized for inducing hypotension, locomotor depression, and inhibition of platelet aggregation ( 61 , 62 ). In turn, NUCs and PDEs are involved in the cleavage of nucleic acid derivatives and realigned substrates, such as ATP, ADP, and AMP.…”