Fig. 3

AMP and G6P bind at two distinct allosteric sites. a Close-up view of the superposed allosteric sites of T-state MtbPYK (yellow) and R-state MtbPYK-OX/AMP/G6P (cyan). The polypeptide chain is shown as a cartoon while interacting residues are shown as sticks. Allosteric effectors AMP and G6P are shown with an unbiased Fo–Fc electron-density map contoured at 3.0 σ (grey). Water molecules are shown as red spheres. Interactions between ligands and the R-state structure are indicated by dashed lines. The T-shaped stacking (or CH–π hydrogen bonding) interactions formed between the adenine ring of AMP and MtbPYK residues (Phe373, Trp398, Met425) are shown by pink dashed lines. Secondary structures that are involved in the interactions with effectors are indicated. The conformational changes of the C-terminal tail loop and the side-chain of residue Trp398 are indicated by arrows. The location of the allosteric site within a subunit is shown as a red box in the inset (i). b, Schematic drawing showing the synergistic interactions at the MtbPYK allosteric sites. Residues forming T-shaped stacking (or CH–π hydrogen bonding) interactions with the adenine ring of AMP are indicated in pink, while water molecules are shown as blue circles