"Computational and Functional Characterization of a Hemorrhagic Metalloproteinase Purified from Cerastes cerastes Venom".

Structural and functional aspects of snake venoms metalloproteinases (SVMPs) have been extensively studied due to their role in envenomation. However, in the detection of certain coagulation disorders these biomolecules have been used and applied for the production of new thrombolytic drugs. CcMP-II, a SVMP-II metalloproteinase with a hemorrhagic activity, isolated from the venom of Cerastes cerastes, its sequence of 472 amino acids was identified. Predicted 3D structure showed an arrangement of CcMP-II into two distinct domains: i) a metalloproteinase domain where the zinc-binding motif is found (HXXGHNLGIDH) in addition to the sequence Cys-Ile-Met (CIM) at the Met-turn and ii) disintegrin-like domain containing RGD motif. CcMP-II inhibits platelet aggregation induced by collagen in a dose-dependent manner with an IC value estimated of 0.11 nM. This proteinase inhibits also aggregation of platelet stimulated by collagen even if the metal chelating agents (EDTA and 1, 10-phenontroline) are present suggesting that anti-aggregating effect is not due to its metalloproteinase domain, but to its disintegrin-like domain. Capillary pathological modifications caused by CcMP-II following intramuscular injection have as well been examined in mice. The key morphological alterations of the capillary vessels were clearly apparent from the ultrastructural study. The CcMP-II can play a key function in the pathogenesis of disorders that occurs following envenomation of Cerastes cerastes. The three-dimensional model of CcMP-II was built to explain structure-function relationships in ADAM/ADAMTs, a family of proteins having significant therapeutic potential. In order to explain structure-function relationships in ADAM / ADAMT, a family of proteins with considerable therapeutic potential, the three-dimensional model of CcMP-II was constructed.