MOLECULAR DOCKING OF CC2-PLA2, A PHOSPHOLIPASE A2-DERIVED FROM CERASTES CERASTES VENOM WITH ITS INHIBITORS

Abstract

Abstract

The current study reported a structure-based molecular docking of Cc2-PLA2, a phospholipase A2 purified from Cerastes cerastes venom by three chromatographic steps. Its molecular weight was equal to 13,534.16 Da and its sequence identified by proteomic analysis consists of 120 amino acid residues. Structurally, when modeled by homology, Cc2-PLA2 3D structure appeared organized into 2 β-strands (11%), 3 α-helices (42%) and 11% disordered structure. To explore their inhibitory effect against Cc2-PLA2 enzymatic activity, curcumin and its analogs, derived from chemical modification of curcumin, were submitted to a molecular docking study. Our results show that all of the curcumin, tetrahydrocurcumin and dihydrocurcumin interact with Cc2-PLA2 by a hydrogen bond established with His47. Moreover, hexahydrocurcumin targeted the residue Asp48 of Cc2-PLA2. Besides this, among all compounds, the most potent complexes were established with hexahydrocurcumin and tetrahdrocurcumin as they show the most negative energies of interaction. This result shows that chemical modification of curcumin promoted its affinity to Cc2-PLA2 and therefore, potentiates the inhibitory effect. His47and Asp48being involved in the catalytic loop of Cc2-PLA2 thus reinforce the obtained results and confirm the inhibitory effect of the studied compounds against the catalytic activity of our enzyme on its specific substrates. The current study opens perspectives for the design of new snake venom-phospholipase A2 inhibitors and the improvement of envenomation therapy.