Destabilase, the novel epsilon-(gamma-Glu)-Lys isopeptidase with thrombolytic activity.
The salivary gland secretion of the leech Hirudo medicinalis contains the enzyme destabilase which hydrolyses epsilon-(gamma-Glu)-Lys cross-links in stabilized fibrin. Accumulation of Glu residues instead of the original Gln residues leads to spontaneous depolymerization of destabilized fibrin. L-gamma-Glu-p-nitroanilide; L-gamma-Glu-dansylcadaverine and isopeptide epsilon-(gamma-Glu)-Lys are low-molecular-weight substrates of destabilase. Destabilase probably exists in molecular forms of molecular weight 50,000, 25,000 and 12,300. The protein part of destabilase is covalently bound to a lipid component of molecular weight 390, which has little cross-reactivity to 6-keto-prostaglandin F1 alpha antiserum. The lipid component ensures the hydrophobic properties of destabilase, inhibition of platelet aggregation, protection from proteolysis and absorption from the intestine into blood during oral administration to experimental animals. It also ensures the protective antithrombotic effect. Almost total (80-100%) thrombolysis of preformed thrombus in the rat was achieved by destabilase 70-100 h after i.v. injection or oral administration.
Baskova
I P
IP
Department of Biology, Moscow State University, USSR.
Nikonov
G I
GI
D000818:Animals; D010450:Endopeptidases / Q000302:isolation & purification* / Q000378:metabolism / Q000627:therapeutic use; D005337:Fibrin / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000302:isolation & purification* / Q000627:therapeutic use; D007700:Kinetics; D007865:Leeches / Q000201:enzymology*; D011489:Protein Denaturation; D051381:Rats; D012471:Salivary Proteins and Peptides / Q000302:isolation & purification / Q000378:metabolism; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000517:prevention & control
D005343:Fibrinolytic Agents; D012471:Salivary Proteins and Peptides; D005337:Fibrin; D010450:Endopeptidases; C045348:fibrin destabilase