Fig. 5: GLUT3 is predicted to bind TMZ and CAPE directly.

The amino acid sequence with the assignment of secondary structures (A) and the three-dimensional structure of GLUT3 (B). The transmembrane region of GLUT3 contains 12 transmembrane segments (TMs) folded into the N-terminal and C-terminal domains, each consisting of two 3-TM repeats. IC1–4 are helices connecting the N-terminal and C-terminal domains. IC1-4 and the C-terminal helix IC5 constitute the intracellular helical (ICH) domain. The corresponding TMs of the four 3-TM repeats are colored the same. In this way, the same blue-violet-green color scheme was used for each 3-TM repeat sequence. The overall docking structure of GLUT3 with D-glucose (C), TMZ (D), or CAPE (E) was simulated using AutoDock Vina software. F The binding energy of the docking model of GLUT3 with glucose/TMZ/CAPE. G Representative snapshots of molecular dynamics (MD) simulation of GLUT3 with TMZ (upper panel) or CAPE (lower panel) at different time points. H Rg values of GLUT3 in GLUT3-TMZ (left panel) and GLUT3-CAPE (right panel) complexes during the 100 ns simulations. I RMSD of GLUT3-TMZ (left panel) and GLUT3-CAPE (right panel) complexes obtained from 100 ns MD simulation. The RMSD of GLUT3-TMZ and GLUT3-CAPE is shown in red and blue, respectively. J RMSF of GLUT3 amino acid residues in GLUT3-TMZ (left panel) and GLUT3-CAPE (right panel) complexes, respectively. The RMSF of GLUT3-TMZ and GLUT3-CAPE are shown in red and blue, respectively. K SASA of GLUT3-TMZ (left panel) and GLUT3-CAPE (right panel) complex. The SASA of GLUT3-TMZ and GLUT3-CAPE are shown in red and blue, respectively. L The secondary structures analysis of GLUT3 in complex with TMZ (left panel) and CAPE (right panel), respectively. White for Coil, black for β-bridge, green for Bend, yellow for Turn, dark blue for α-Helix, purple for 5-Helix, and grey for 3-Helix. All structure figures were prepared with PyMOL.