Biochemical characteristics of fibrolase, a fibrinolytic protease from snake venom.
Fibrolase, a fibrinolytic enzyme isolated from Agkistrodon c. contortrix (southern copperhead) venom, solubilizes fibrin primarily by rapid hydrolysis of the alpha and beta chains. Fibrolase is also an A alpha, B beta fibrinogenase. The breakdown products of fibrin and fibrinogen following incubation with fibrolase were different from those observed with plasmin. This enzyme is a metalloprotease that was inhibited by ethylenediaminetetraacetic acid. Fibrolase was inhibited by dithiothreitol, suggesting that disulfide bonds are important for catalytic activity. It was also inhibited by alpha 2-macroglobulin, but not by the soybean or lima bean trypsin inhibitors, diisopropylfluorophosphate, or p-hydroxymercuribenzoate. Unlike thrombolytic agents such as streptokinase, fibrolase does not activate plasminogen as evidenced by the use of plasmin-specific chromogenic substrate S-2251 and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Marion Merrell Dow Inc., Kansas City, Mo.
N K
NK
Ahmed
K D
KD
Tennant
F S
FS
Markland
J P
JP
Lacz
D000818:Animals; D002364:Caseins / Q000378:metabolism; D003435:Crotalid Venoms / Q000032:analysis*; D004229:Dithiothreitol / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D013917:Thrombin / Q000302:isolation & purification / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000494:pharmacology
D002364:Caseins; D003435:Crotalid Venoms; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D009842:Oligopeptides; D000511:alpha-Macroglobulins; C026018:azocasein; C018788:valyl-leucyl-lysine 4-nitroanilide; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D004492:Edetic Acid; D013917:Thrombin; D008666:Metalloendopeptidases; C058789:fibrolase; D004229:Dithiothreitol