Fig. 5: Effect of POA on PanDWT and resistant mutant, non-POA binding PanD127TRASC131 as determined by dynamic light scattering.
From: Pyrazinamide triggers degradation of its target aspartate decarboxylase
a The distribution of the intensity of dynamic light scattering by PanDWT without drug (black) and PanDWT with 200 µM POA (red) as a function of particle diameter (d in nm) shows that PanDWT transforms into higher oligomers (P1–4) upon addition of POA with calculated hydrodynamic diameters of 21.04 ± 7.22, 55.04 ± 6.35, 955.4 ± 106.9, and 4801 ± 1134 nm, respectively. The estimated intensities of peaks 1–4 were 11%, 8%, 38%, and 43%, respectively. b In contrast, the PanD127TRASC131 mutant retained its prominent peak at around 11.5 nm in the presence (red) of 200 μM POA (drug-free control: black). Experiments were repeated three times yielding the same results. The results from a representative experiment are shown. These data show that POA causes oligomer formation of wild-type PanD but not of a POA-resistant mutant version of the protein. These results suggest that the drug does not cause protein aggregation per se. Source data are provided as a Source Data file.
