Molecular modeling,biochemical characterization,and pharmacological properties of Cc3‐SPase: A platelet‐aggregating thrombin‐like enzyme purified from Cerastes cerastes venom

Cc₃‐SPase (30 kDa‐proteinase; pI 5.98) was isolated from Cerastes cerastes venom. Its sequence of 271 residues yielded from LC‐MALDI‐TOF showed high degrees of homology when aligned with other proteinases. Cc₃‐SPase cleaved natural and synthetic proteins such as casein and fibrinogen leaving fibrin clots unaffected. Cc₃‐SPase was fully abolished by ion chelators, whereas aprotinin, antithrombin III (Sigma Aldrich, Saint‐Louis, Missouri, USA), and heparin were ineffective. Affinity of Cc₃‐SPase to benzamidine indicated the presence of an aspartate residue in the catalytic site as confirmed by three‐dimensional structure consisting of 14 β‐strands and four α‐helices. Molecular mechanisms revealed that Cc₃‐SPase is capable of promoting dysfunctional platelet aggregation via two signaling pathways mediated by the G‐coupled protein receptors and αIIbβ3 integrin. Cc₃‐SPase is involved in both extrinsic/intrinsic coagulation pathways in deficient plasmas by replacing defective/lacking factors FII, FVII, and FVIII but not FX. Cc₃‐SPase could substitute missing factors in blood diseases related to plasma factor deficiencies.