Figure 1.
Summary of stability data for FVIII Arg121Cys/Leu2302Cys or Ala108Ile in combination with A2 domain interface mutations. FVIII thermal decay (A), chemical stability (B), and FVIIIa spontaneous decay (C) for Asp519Ala, Asp519Val, Glu665Ala, Glu665Val, Glu1984Ala, Glu1984Val, or Asp519Val/Glu665Val mutants (open bars) and the variants where each of these mutants were combined with either Ala108Ile (solidbars)or Arg121Cys/Leu2302Cys (grey bars) are shown. The first order rate constants for FVIII thermal decay of WT and mutants FVIII (4 nM) at 57°C, IC50 for guanidinium, and the first order rate constants for FVIIIa decay were obtained by methods previously described [8]. For FVIII thermal decay (A) or FVIIIa decay (C) bar heights correspond to stability index values obtained by dividing the decay rate of WT by that of the variant. For guanidinium denaturation (B) results are expressed as relative IC50 values as compared with WT FVIII. Each bar represents the value averaged from three separate determinations and standard deviation values were drawn.