Identification and inhibitory activity against α-thrombin of a novel anticoagulant peptide derived from oyster (Crassostrea gigas) protein

Abstract

A newly discovered anticoagulant peptide was isolated, purified and identified from the pepsin hydrolysate of oyster (Crassostrea gigas) which could potently prolong the activated partial thromboplastin time and the thrombin time. The anticoagulant peptide with a 1264.36 Da molecular mass was similar to the amino acid sequence of the C-terminal segment (DFEEIPEEYLQ) of hirudin (a potent thrombin inhibitor). The peptide specifically inhibited a vital blood coagulation factor: thrombin. The molecular docking energy scores of the anticoagulant peptide with the active site, exosite-I and exosite-II of thrombin were 132.355 kcal mol-1, 151.266 kcal mol-1 and 147.317 kcal mol-1, respectively. The anticoagulant peptide interacted with thrombin by competing with fibrinogen for an anion-binding exosite I. In the anticoagulant peptide-thrombin complex, there are seven hydrogen bonds and reciprocity exists between hydrogen atoms and oxygen atoms, and electrostatic and hydrophobic interactions are also involved. Such abundant interactions may be accountable for the high affinity and specificity of the anticoagulant peptide.