Figure 3: Ce-2d traps iPGM in an open conformation.

(a) One subunit of the asymmetric unit showing the binding mode of the Ce-2d macrocycle to C. elegans iPGM. The Mn²⁺ and Zn²⁺ ions are represented as blue and tan spheres, respectively, and the bound macrocycle is drawn as CPK space-filling spheres in a cavity defined by iPGM residues within 5 Å (transparent spheres). (b) Superposition of C. elegans iPGM-o (cyan), C. elegans iPGM-m (tan) and C. elegans iPGM·Ce-2d (aquamarine). The Ce-2d peptide is represented as cylinders. (c) Macrocycle (cylinders) positioned within a cleft of iPGM represented as an electrostatic surface. (d) CPK space-filling representations of Ce-2d illustrating the ‘capping’ orientation of the five tyrosine residues (1, 3, 7, 9 and 11) and (e) the edge-to-face interaction of Tyr 1 and 9. Additional residues are indicated.