Fig. 1

Structure of MtbPYK and overview of three allosteric sites of PYK. a Crystal structure of the MtbPYK-OX/AMP/G6P complex (PDB ID 5WSB) in the synergistically activated R-state. Two orthogonal views of MtbPYK-OX/AMP/G6P show the tetramer architecture, domain boundaries, active site and synergistic effector sites. The A–A (large) and C–C (small) interfaces between subunits are shown as dashed lines. Each subunit comprises three domains, and one subunit (chain A) is coloured to show the domains: A-domain in green (residues 1–70, 168–336), B-domain in yellow (residues 71–167), C-domain in cyan (residues 337–472). The N terminus and C terminus of this subunit are indicated. Polypeptide chains are shown as cartoons, while metals and ligands are represented by spheres. Mg²⁺ and K⁺ located at the active site (brown box) are coloured in green and purple, respectively. The oxalate molecule (OX) at the active site is associated with the Mg²⁺. The canonical allosteric site (AMP-bound) is indicated by the purple box, while the newly discovered G6P-binding site (synergistically coordinating with the AMP-binding site) is shown by the magenta box. The AMP-binding loop (AMP loop) and G6P-binding loop (G6P loop) are coloured black. The C-terminal loop (tail loop) which undergoes a conformational change in the transition of inactive- and active states is indicated. b A surface representation of the PYK monomer (A-, B- and C-domains) highlighting three allosteric effector sites: canonical allosteric site that binds AMP, F26BP or F16BP; amino-acid site found in mammalian M1/M2PYK that binds amino acids as a nutrient sensor; sugar monophosphate site that binds G6P in M. tuberculosis synergistically coordinating with the canonical site, and probably binds R5P or G3P in some organisms. The A-, B- and C domains are shown in green, yellow and cyan, respectively. Effector-site ligands are shown as spheres