Fig 13.
(A) Plot of the hypothetical Btotal(τ) (gray) and c(τ) for PCSK9 and PCSK9-LDL-R binding at a fixed PCSK9 L0 = 1 nM, Λ = 5 min (ki = k−i = 1x10-2 s-1), and the kon and koff values given in Table 2 (solid lines color-coded as follows: wt/pH 7.4 dark blue (not visible); wt/pH 5.3 purple; D374Y/pH 7.4 cyan; D374Y/pH5.3 green), and Bfree(τ) (dotted lines color coded the same as c(τ)). Simulated occupancy is essentially zero for both wt and mutant PCSK9 at neutral pH, whereas negligible nSSO is achieved at low pH. (B) Same as A, except L0 = 0 nM. Moderate nSSO is achieved at low pH (maximum occupancy = 68% versus 75% for the wt and mutant forms, respectively). (C) Same as A, except L0 = 40.5 nM. High nSSO is achieved at low pH, where the gap between wt and mutant forms narrows to only a few percent at all time points (maximum occupancy = 82% versus 85% for the wt and mutant forms, respectively).