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Literature summary for 3.4.21.7 extracted from

  • Nogami, K.; Nishiya, K.; Saenko, E.L.; Takeyama, M.; Tanaka, I.; Yoshioka, A.; Shima, M.
    Identification of a plasmin-interactive site within the A2 domain of the factor VIII heavy chain (2008), Biochim. Biophys. Acta, 1784, 753-763.
    View publication on PubMed
Search for more literature for 3.4.21.7

Activating Compound

Activating Compound Comment Organism Structure
Factor IXa regulates plasmin-catalyzed factor VIIIa inactivation Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information active-site modified plasmin (Ah-plasmin) lacking enzymatic activity. Factor VIII binds with higher affinity than the A2 subunit to Ah-plasmin. The intact heavy chain also binds with ca. 10fold higher affinity than the light chain. Binding affinity of the R484A mutant of A2 subunit of factor VIII to Ah-plasmin is ca. 250fold lower than that of wild-type A2. A2 mutants (K377A, K466A, and R471A) also exhibit reduced binding affinity (by 10-20fold) compared with wild-type A2 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
479-504 peptide of factor VIII blocks A2 subunit binding to Ah-plasmin by ca. 50% in a dose-dependent manner Homo sapiens
484-509 peptide of factor VIII blocks A2 subunit binding to Ah-plasmin by ca. 50% in a dose-dependent manner Homo sapiens
489-514 peptide of factor VIII weakly inhibits binding of the A2 subunit and plasmin with ca. 80% residual binding at the highest concentration (0.8 mM) of peptide Homo sapiens
6-aminohexanoic acid blocks the interactions between light chain and plasmin in a dose-dependent manner by more than 90%. Blocks A2 subunit and plasmin interaction weakly by ca. 30%. Inhibitory effect of 6-aminohexanoic acid on the interaction between the heavy chain or factor VIII and Ah-plasmin is similar to that for the A2 interaction Homo sapiens
A2 subunit of factor VIII plasmin-catalyzed activation of factor VIII is significantly inhibited by the addition of isolated A2 subunit of factor VIII in a dose-dependent manner Homo sapiens
Ah-plasmin immobilized Ah-plasmin inhibits the A2 binding to Ah-plasmin by ca. 80% in a dose-dependent manner Homo sapiens
mAb413 antibody of A2 subunit, that blocks plasmin-catalyzed factor VIII heavy chain cleavage at Arg336 and Arg372, but not at Arg740. This antibody does not affect plasmin-catalyzed cleavage of the light chain Homo sapiens
pefabloc
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 Homo sapiens
R484A mutant of A2 subunit of factor VIII, possessing ca. 250fold reduced affinity for plasmin, weakly inhibits factor VIIIa inactivation by ca. 20% Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
factor VIII + H2O plasmin catalyzes activation or inactivation of factor VIII. The A2 domain of factor VIII, in particular residue Arg484, contributes to a unique plasmin-interactive site within the heavy chain that promotes plasmin docking during cofactor inactivation cleavage of the heavy chain Homo sapiens ?
-
 ?

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0057
-
 479-504 peptide of factor VIII
-
 Homo sapiens
0.0068
-
 6-aminohexanoic acid blocked interaction between light chain and plasmin Homo sapiens
0.0103
-
 484-509 peptide of factor VIII
-
 Homo sapiens
0.0113
-
 6-aminohexanoic acid blocked interaction between A2 subunit and plasmin Homo sapiens
0.0628
-
 489-514 peptide of factor VIII
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000151
-
-
 Homo sapiens Ah-plasmin