MOLECULAR DOCKING OF SUBTILISIN K2, FIBRIN DEGRADING ENZYME FROM INDONESIAN MOROMI WITH FIBRIN SUBSTRATE

Fibrinogen supplies the primary building block of the blood clot or thrombus after α-thrombin converts this fibrinogen to fibrin during the final phases of coagulation. When the homeostasis system is disrupted, blood clots that aggregate in the blood vessels can lead to thrombosis. Fibrin degrading enzyme from Bacillus subtilis K2 (Subtilisin K2) has many excellent characteristics with strong fibrinolytic activity. Bioinformatic analysis indicated that the enzyme molecule appeared to share conserved domain, with peptidase s8 super family also known as the subtilase family with its motif: Asp subtilase (motif: VAVIDSGIDSsH), His subtilase (motif: HGTHVAGTIAA) and Ser subtilase (motif: GTSMATPHVAG). Study on molecular docking between this fibrin degrading enzymes and the specific substrates, fibrin and fibrinogen was aimed to predict the mechanism of action. This analysis, revealed no productive interaction between Subtilisin K2 and fibrinogen. However, hydrolysis reaction is indicated strongly between Subtilisin K2 and fibrin substrate. Amino acid Asp19, His51, and Ser208 in the Subtilisin K2’s active site interacted with Leu168, Ile171, and Leu172 of the fibrin substrate with ∆G of –19.4 kcal/mol that showed suitable substrate specificity. The fibrin degrading enzyme Subtilisin K2 tend to act more as fibrin degrading enzyme than as fibrinogen degrading enzyme.