Figure 7
Sequence differences in the binding pocket of related phosphite and hypophosphite PBPs change the shape and orientation of the ligand binding site. (A) Sequence conservation in the binding pocket and mode of binding of phosphite in HtxB (green) and PtxB (pink). The protein is drawn as a cartoon, with the ligands and side chains drawn as sticks. The P-H…π interaction is drawn as a blue dashed line. (B) A view of the relative orientation of the π system that provides ligand specificity. The view is rotated 90° relative to (A), with the positions of W52 and Y203 shown as sticks above the phosphite. The molecular surface of the binding pocket is shown in grey. (C) The fold and conformation of the two proteins is largely conserved. The protein backbones are represented as a cartoon and the ligands as spheres. (D) The mode of binding of phosphite in HtxB and PtxB are mirror-images of each other. The phosphite molecules are shown as sticks and the relative position and interactions with W52 and Y203 are indicated schematically with circles and dashed lines, respectively. (E) The volume of the binding pocket (shown as an enclosed surface) in (i) HtxB (orange), (ii) modelled HtxB-hybrid (grey) and (iii) an overlay of the two volumes. Sequence differences around the binding pocket generate more space in the hybrid. The position of hypophosphite in the HtxB structure is shown for reference.
