Figures & data
Figure 1. Chemical structures of ligands docked on sulfotranferases.
Figure 2. Chromatograms of (A) blank rabbit plasma, (B) plasma spiked with 1 μg/mL BR-AEA, and (C) plasma sample obtained from a rabbit at 7 h after i.v. administration of BR-AEA (0.1 mg/kg).
Table 1. Precision and accuracy of BR-AEA in rabbit plasma (n = 3).
Figure 3. Plasma concentration–time disappearance curve of BR-AEA in rabbits following i.v. administration of 0.1 mg/kg BR-AEA. Each data point represents mean ± standard deviation (n = 6).
Table 2. Pharmacokinetic parameters of BR-AEA (n = 6) and R-salbutamol (0.1 mg/kg, i.v.).
Figure 4. Binding sites for (A) dopamine, (B) salbutamol, and (C) BR-AEA on SULT1A3. The 100 conformations with lowest energy at interaction are represented as spheres. Dopamine and 3′-phosphoadenosine 5′-phosphate (PAPS) are depicted with the coordinates found in the crystallized structure (PDB code: 2A3R). Ligands are depicted in the lowest free energy complex. BR-AEA does not have moieties exposed for enzyme sulfatation from PAPS.
Figure 5. Binding of BR-AEA on SULTs. (A) BR-AEA on SULT1A3; (B) BR-AEA on SULT1C1; (C) a closer view of the binding site for salbutamol (aquamarine bonds) and BR-AEA (in stick and ball representation) on SULT1A3. PAPS and dopamine were built with coordinates from the models (PDB codes: 2A3R and 2ETG) and are shown as green bonds. Residues reported in the binding site are labeled. Interaction of hydroxyl groups bonded with Glu146 to the boron atom can be visualized.
Table 3. Kd values of SULT substrates on SULT1A3, SULT1C1, and SULT1A1 with computational docking.