Fig. 3: Entropy-driven binding of inhibitors 1–4 with EcGUS and BdGUS.
a Graphical presentation to show the thermodynamic parameters of the binding interactions of EcGUS and BdGUS in complex with inhibitors 1–4 at 298 K. The detailed analysis is shown in Supplementary Table 1. a 250 mM NaCl, 20 mM KH2PO4, 100 mM Na2HPO4, pH 8.0. b 250 mM NaCl, 20 mM Tris, pH 8.0. b Cartoon presentation to demonstrate that several water molecules (represented by red circles) are orderly located at the active site of gut bacterial GUSs, as shown in EcGUS (the left model), and can be displaced by binding with UIFGs. The best inhibitor, C6-nonyl UIFG, displays tight binding with EcGUS (Ki = 4.5 nM) and 23,300-fold higher selectivity for EcGUS than for human GUS (the bottom right). GUSs are mainly different in the aglycone-binding site, which can be leveraged to develop selective inhibitors. If UIFGs have no substitution (the top right), selective inhibition no longer exists.
