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.