Fig. 5: Sugar-coupling analysis of PfHT1 and rat GLUT5.
a, Normalized STD effects and transport activity of sugar binding residue mutants of PfHT1 in the presence of D-glucose or 2,5-AHM. Bars: STD effects; circles: percentage of sugar transport compared to WT for D-glucose and 2,5-AHM, with previously determined values (asterisk, as reported in ref. 19). b, Left: surface representation cross-section of the 2,5-AHM bound fully occluded (wheat) X-ray structure of PfHT1. Right: surface representation cross-section of the 2,5-AHM bound inward-occluded (blue) structure of PfHT1 obtained by cryo-EM. Ligand shown as sticks. c, Left: binding site in the cryo-EM structure of PfHT1 in complex with 2,5-AHM (blue sticks) in the inward-occluded conformation. Right: comparison of the 2,5-AHM coordination between the fully occluded PfHT1 X-ray structure (2,5-AHM as pink sticks, interacting residues and helices as cyan, yellow and gray) to inward-occluded cryo-EM complex (shown as on left). Hydrogen bond interactions are indicated by dashed lines. d, Overall structural comparison of the PfHT1 2,5-AHM complexes in the fully occluded and inward-occluded states colored as in c. Upon inner gate open/closing the substrate would be displaced vertically by ~2 Å. e, The gating residues in the 2,5-AHM X-ray complex structure of PfHT1 (yellow sticks, with protein and ligand shown as in c) compared to GLUT5. Right: comparison with rat GLUT5 (green) (PDB 4YBQ). f, Normalized STD effects for WT and mutants of rat GLUT5 in the presence of D-fructose; bars: STD effect values, circles: percentage of sugar transport compared to WT, with values determined previously (asterisks) taken from ref. 25 or as shown in Extended Data Fig. 7b.
