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Proc Natl Acad Sci U S A. 1987 Jun; 84(12): 4031–4034.
PMCID: PMC305015

The reciprocal effects of epsilon-aminohexanoic acid and chloride ion on the activation of human [Glu1]plasminogen by human urokinase.


The activation of human [Glu1]plasminogen [( Glu1]Pg) by high-molecular-weight two-chain human urinary urokinase [EC and low-molecular-weight two-chain human urinary urokinase is inhibited by Cl- at physiological concentrations and stimulated by epsilon-aminohexanoic acid (epsilon Ahx; epsilon-aminocaproic acid). The inhibition by Cl- does not occur in the presence of concentrations of epsilon Ahx that saturate the acid's weak binding sites on [Glu1]Pg, and the stimulation by epsilon Ahx is maximally exhibited in the presence of Cl-. We have used intrinsic fluorescence measurements with [Glu1]Pg to show that the conformational alteration and the concomitant increase in activation rate that accompanies epsilon Ahx-binding to [Glu1]Pg in the presence of Cl- does not occur in the same manner without Cl-. Further, the decrease in the intrinsic fluorescence that is attendant to Cl- binding to [Glu1]Pg in the absence of epsilon Ahx is not observed in the presence of this effector molecule. Analyses of the results of this manuscript strongly indicate that a conformation of [Glu1]Pg that is not optimal for its activation by urokinase is adopted in the presence of Cl-, and this is relieved by epsilon Ahx. This has important implications in the inhibition of [Glu1]Pg activation in the solution phase of blood plasma and in the large acceleration of this process when plasminogen is bound to physiological positive effectors via its epsilon Ahx-binding site(s).

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Selected References

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  • Wiman B. Primary structure of peptides released during activation of human plasminogen by urokinase. Eur J Biochem. 1973 Nov 1;39(1):1–9. [PubMed]
  • Wiman B. Primary structure of the B-chain of human plasmin. Eur J Biochem. 1977 Jun 1;76(1):129–137. [PubMed]
  • Malinowski DP, Sadler JE, Davie EW. Characterization of a complementary deoxyribonucleic acid coding for human and bovine plasminogen. Biochemistry. 1984 Aug 28;23(18):4243–4250. [PubMed]
  • Markus G, DePasquale JL, Wissler FC. Quantitative determination of the binding of epsilon-aminocaproic acid to native plasminogen. J Biol Chem. 1978 Feb 10;253(3):727–732. [PubMed]
  • Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of omega-aminocarboxylic acids. Biochim Biophys Acta. 1975 May 30;393(1):55–65. [PubMed]
  • Moroi M, Aoki N. Isolation and characterization of alpha2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis. J Biol Chem. 1976 Oct 10;251(19):5956–5965. [PubMed]
  • Violand BN, Byrne R, Castellino FJ. The effect of alpha-,omega-amino acids on human plasminogen structure and activation. J Biol Chem. 1978 Aug 10;253(15):5395–5401. [PubMed]
  • Claeys H, Vermylen J. Physico-chemical and proenzyme properties of NH2-terminal glutamic acid and NH2-terminal lysine human plasminogen. Influence of 6-aminohexanoic acid. Biochim Biophys Acta. 1974 Apr 11;342(2):351–359. [PubMed]
  • Chibber BA, Castellino FJ. Regulation of the streptokinase-mediated activation of human plasminogen by fibrinogen and chloride ions. J Biol Chem. 1986 Apr 25;261(12):5289–5295. [PubMed]
  • Brockway WJ, Castellino FJ. Measurement of the binding of antifibrinolytic amino acids to various plasminogens. Arch Biochem Biophys. 1972 Jul;151(1):194–199. [PubMed]
  • Violand BN, Castellino FJ. Mechanism of the urokinase-catalyzed activation of human plasminogen. J Biol Chem. 1976 Jul 10;251(13):3906–3912. [PubMed]
  • Jameson GW, Roberts DV, Adams RW, Kyle WS, Elmore DT. Determination of the operational molarity of solutions of bovine alpha-chymotrypsin, trypsin, thrombin and factor Xa by spectrofluorimetric titration. Biochem J. 1973 Jan;131(1):107–117. [PMC free article] [PubMed]
  • Chibber BA, Morris JP, Castellino FJ. Effects of human fibrinogen and its cleavage products on activation of human plasminogen by streptokinase. Biochemistry. 1985 Jul 2;24(14):3429–3434. [PubMed]
  • Reddy KN, Markus G. Mechanism of activation of human plasminogen by streptokinase. Presence of active center in streptokinase-plasminogen complex. J Biol Chem. 1972 Mar 25;247(6):1683–1691. [PubMed]
  • McClintock DK, Bell PH. The mechanism of activation of human plasminogen by streptokinase. Biochem Biophys Res Commun. 1971 May 7;43(3):694–702. [PubMed]
  • Chibber BA, Radek JT, Morris JP, Castellino FJ. Rapid formation of an anion-sensitive active site in stoichiometric complexes of streptokinase and human [Glu1]plasminogen. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1237–1241. [PMC free article] [PubMed]
  • Kosow DP. Kinetic mechanism of the activation of human plasminogen by streptokinase. Biochemistry. 1975 Oct 7;14(20):4459–4465. [PubMed]
  • Bajaj AP, Castellino FJ. Activation of human plasminogen by equimolar levels of streptokinase. J Biol Chem. 1977 Jan 25;252(2):492–498. [PubMed]
  • Brockway WJ, Castellino FJ. A characterization of native streptokinase and altered streptokinase isolated from a human plasminogen activator complex. Biochemistry. 1974 May 7;13(10):2063–2070. [PubMed]
  • Günzler WA, Steffens GJ, Otting F, Kim SM, Frankus E, Flohé L. The primary structure of high molecular mass urokinase from human urine. The complete amino acid sequence of the A chain. Hoppe Seylers Z Physiol Chem. 1982 Oct;363(10):1155–1165. [PubMed]

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