Biochemistry of cancer procoagulant.
Cancer procoagulant (CP), EC3.4.22.26, is a cysteine proteinase produced by malignant or fetal tissue. It is a single chain Mr 68 kDa protein containing no carbohydrates. Prevalent amino acids are Ser (19.15), Gly (18.7%), Glu (12.5%), Lys (8.1%) and Asp (7.1%). Amino-acid sequence of CP is not determined yet. The natural substrates for CP are coagulation factor X and probably PAR-1 receptor. However, the peptidyl bond in factor X molecule hydrolyzed by CP is different from the bond recognized by other known FX-activators. Peptidyl chromogenic substrates hydrolyzed by CP are those with Pro at P2 and Arg or Lys at P1 position. Factor X-activating activity of CP is inhibited by number of various inhibitors: peptidyl diazomethyl ketones. iodoacetamide, mercuric chloride, PMSF, leupeptin and antipain. It has been demonstrated that E-64, a specific inhibitor of cysteine proteinases, inhibits CP reversible acting as a competitive inhibitor of the enzyme. The CP activity is modulated by the presence of divalent metal ions in the reaction environment. Ca2+, Cd2+, Mg2+ and Mn2+ ions potentiate the procoagulant activity when Cu2+, Fe2+, Sn2+ and Zn2+ ions inactivate CP.
Mielicki
W P
WP
Department of Pharmaceutical Biochemistry, Medical University of Lodz, Poland. wojtek77@friko2.onet.pl
D000818:Animals; D001779:Blood Coagulation Factors / Q000737:chemistry*; D002413:Cations, Divalent / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins; D011817:Rabbits
D001779:Blood Coagulation Factors; D002413:Cations, Divalent; D015853:Cysteine Proteinase Inhibitors; D009363:Neoplasm Proteins; D005170:Factor X; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant