Figure 4.

Effect of naturally occurring VKOR mutations on VKOR activity and KO binding. (A) Cell-based VKOR activity of all naturally occurring VKOR mutations. Each VKOR mutation was transiently expressed in DGKO FIXgla-PC/HEK293 reporter cells; the transfected cells were cultured with 5 µM KO for activity assay. Bar color codes are the same as in Figure 2. Wild-type VKOR activity is indicated by the dotted line. (B) KO concentration titration of wild-type VKOR transiently expressed in DGKO FIXgla-PC/HEK293 reporter cells. The EC₅₀ of KO was determined by GraphPad software. (C) The EC₅₀ of KO for all naturally occurring VKOR mutations. Data are presented as mean ± SD. Bar color codes are the same as Figure 2. The EC₅₀ of the wild-type VKOR is indicated by the dotted line. (D) Correlation between IC₅₀ of warfarin and EC₅₀ of KO for naturally occurring VKOR mutations. Data for the Y139H mutant were excluded for the correlation calculation.