The role of enzymatic activity in inhibition of the extrinsic tenase complex by phospholipase A2 isoenzymes from Naja nigricollis venom.
Three phospholipase A2 isoenzymes from Naja nigricollis venom inhibit the extrinsic tenase complex. We examined the role of their enzymatic activity in this inhibition by studying the effects of native and His-modified enzymes. Only CM-IV of the His-modified, catalytically inactive proteins showed significant inhibition of the activity of the complex. This indicates that strongly anticoagulant CM-IV inhibits the complex by both enzymatic and nonenzymatic mechanisms, whereas the weakly anticoagulant isoenzymes, CM-I and CM-II, inhibit primarily by catalytic degradation of phospholipids. This indicates a functional difference in the mode of inhibition between strongly and weakly anticoagulant phospholipase A2 enzymes.
Kini
R M
RM
Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Richmond 23298, USA.
Evans
H J
HJ
D000818:Animals; D002417:Cattle; D004546:Elapid Venoms / Q000201:enzymology*; D017815:Elapidae; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000633:toxicity*; D065427:Factor Xa Inhibitors; D006639:Histidine / Q000737:chemistry; D007527:Isoenzymes; D008074:Lipoproteins / Q000187:drug effects* / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism / Q000633:toxicity*; D054467:Phospholipases A2; D013925:Thromboplastin / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology
D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D065427:Factor Xa Inhibitors; D007527:Isoenzymes; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D014812:Vitamin K; D006639:Histidine; D013925:Thromboplastin; D010741:Phospholipases A; D054467:Phospholipases A2