American Society of Hematology

Figure 1.

$Figure 1. Structure and function of PK-R and AG-348. (A) Simplified schematic of glycolysis. (B) Chemical structure of AG-348. (C) Activity of recombinant PK-R enzyme incubated with indicated concentrations of AG-348 (PEP = 0.065 mM). Mean, standard deviation, range, and number of experimental replicates are indicated in the column on right-hand side of panel. (D) Plot of activity of recombinant WT PK-R enzyme stimulated with PEP with or without preincubation by AG-348 (5 μM); the average of 3 technical replicates is shown. (E) Ribbon diagram of the cocomplex crystal structure of PK-R tetramer bound to AG-348 (shown as space-filling model in gray). PEP (blue) and FBP (brown) also shown as space-filling models. Diffraction statistics are shown below the diagram. (F) Model of AG-348 in PK-R allosteric- binding pocket illustrating key interactions. All error bars are standard deviations. ADP, adenosine diphosphate; PG, phosphoglyceric acid.$

Structure and function of PK-R and AG-348. (A) Simplified schematic of glycolysis. (B) Chemical structure of AG-348. (C) Activity of recombinant PK-R enzyme incubated with indicated concentrations of AG-348 (PEP = 0.065 mM). Mean, standard deviation, range, and number of experimental replicates are indicated in the column on right-hand side of panel. (D) Plot of activity of recombinant WT PK-R enzyme stimulated with PEP with or without preincubation by AG-348 (5 μM); the average of 3 technical replicates is shown. (E) Ribbon diagram of the cocomplex crystal structure of PK-R tetramer bound to AG-348 (shown as space-filling model in gray). PEP (blue) and FBP (brown) also shown as space-filling models. Diffraction statistics are shown below the diagram. (F) Model of AG-348 in PK-R allosteric- binding pocket illustrating key interactions. All error bars are standard deviations. ADP, adenosine diphosphate; PG, phosphoglyceric acid.

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