Figure 1
Models of the inward- and outward-facing conformations of GLUT3 showing the sites of selected docked ligands from the target-based virtual screening (TBVS). Overview of the GLUT3 models for the inward-facing (A) and outward-facing (B) conformations showing the glucose binding site (glucose as stick model, colored black). The rainbow coloring of the protein ribbon diagram starts with blue at the N-terminus and ends with red at the C-termius. Close-up of the glucose binding site in the inward-facing (C) and outward-facing (D) conformations of GLUT3. Glucose modeling was based on the glucosyl moiety of nonyl beta-D-glucopyranoside from PDB ID 4PYP (C) and alpha-D-glucopyranose-(1–4)-alpha-D-glucopyranose from PDB ID 4ZWC (D). Glucose (yellow) and active site residues (grey) are shown as stick models. Dashed black lines represent hydrogen bond interactions. Side chains of Q159, N286 and W386 (red labels) adopt different conformations in the two conformations. Central slices through the GLUT3 isosurface showing the targeted ligand pockets in the inward-facing (E) and outward-facing (F) conformations. Validated ligand candidates from TBVS are shown as stick models, colored from the highest to the lowest potency as green, blue, and red (see also Table 1). (A,C,E) Homology model for the GLUT3 inward-facing conformation was generated in MOE, using as a template the crystal structure of GLUT1 (PDB ID 4PYP). (B,D,F) Structural model for the outward-facing conformation was the GLUT3 crystal structure PDB ID 5C65. The figures were generated with Pymol (https://www.pymol.org) (A–E) and ChimeraX (https://www.rbvi.ucsf.edu/chimerax) (E–F).
