Phosphodiesterase from Daboia russelli russelli venom: Purification, partial characterization and inhibition of platelet aggregation

• Published in: Toxicon (Oxford) 2014-09, Vol.88, p.1-10
• Main Authors: Mitra, Jyotirmoy, Bhattacharyya, Debasish
• Format: Article
• Language: English
• Subjects: Agglomeration; Animals; Daboia; Daboia russelli russelli; Enzyme inhibition; Enzymes; Homogeneity; Humans; Inhibitors; Ion exchangers; Partial differential equations; Phosphodiesterase; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - isolation & purification; Phosphoric Diester Hydrolases - pharmacology; Plant Extracts - pharmacology; Platelet aggregation; Platelet Aggregation - drug effects; Platelets; Signalling; Snake venom; Viper Venoms - chemistry
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2014.06.004

Phosphodiesterases (PDEs) belong to a super-family of enzymes that have multiple roles in the metabolism of extracellular nucleotides and regulation of nucleotide-based intercellular signalling. A PDE from Russell's viper (Daboia russelli russelli) venom (DR-PDE) was purified by gel filtration, ion exchange and affinity chromatographies. Homogeneity of the preparation was verified by SDS-PAGE, SE-HPLC and mass spectrometry. It was free from 5′-nucleotidase, alkaline phosphatase and protease activities. Identity of the enzyme was ensured from partial sequence homology with other PDEs. DR-PDE was inactivated by polyvalent anti-venom serum and metal chelators. The enzyme was partially inhibited by the root extracts of four medicinal plants but remained unaffected by inhibitors of intracellular PDEs. DR-PDE hydrolyses ADP and thus, strongly inhibits ADP-induced platelet aggregation in human platelet rich plasma. This study leads to better understanding of a component of Russell's viper venom that affects homoeostatic system of the victim. [Display omitted] •Phosphodiesterase (DR-PDE) from Daboia russelli russelli venom is a 100 kDa metalloenzyme.•DR-PDE strongly inhibits ADP induced aggregation of human blood platelets.•Catalytic activity of DR-PDE is completely neutralised by anti-venom serum.•Root extracts of selected medicinal plants show promising inhibitory activity towards DR-PDE.•DR-PDE activity remains unaffected by intracellular PDE inhibitors.