9SDL
Cryo-EM structure of PfHT1 bound to 2,5-anhydro-D-mannitol
This is a non-PDB format compatible entry.
Summary for 9SDL
| Entry DOI | 10.2210/pdb9sdl/pdb |
| EMDB information | 54787 |
| Descriptor | Hexose transporter 1,Green fluorescent protein, 2.5-anhydro-D-mannitol (2 entities in total) |
| Functional Keywords | sugar transporter, plasmodium falciparum hexose transporter 1, transport protein |
| Biological source | Plasmodium falciparum (malaria parasite P. falciparum) More |
| Total number of polymer chains | 2 |
| Total formula weight | 169608.09 |
| Authors | Gulati, A.,Suades, A.,Drew, D. (deposition date: 2025-08-14, release date: 2026-04-15, Last modification date: 2026-04-29) |
| Primary citation | Ahn, D.H.,Alleva, C.,Reichenbach, T.,Gulati, A.,Ruda, A.,Bonaccorsi, M.,Silberberg, J.M.,Claesson, M.,Suades, A.,Delemotte, L.,Widmalm, G.,Drew, D. A two-step mechanism for sugar translocation. Nat.Struct.Mol.Biol., 33:652-663, 2026 Cited by PubMed Abstract: In mammals, glucose transporters (GLUTs) mediate organism-wide sugar distribution, yet the molecular basis of substrate specificity remains unclear. The bacterial xylose transporter XylE serves as a model for GLUTs. However, although xylose and glucose bind with a similar affinity, xylose is transported, but glucose acts as an inhibitor. Here, using saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, we distinguished transported sugars from sugar inhibitors. Our findings revealed that only transported sugars generate STD NMR signals, which are abolished for xylose when XylE is trapped in either outward- or inward-facing conformations. Engineering the sugar-binding pocket and gating helix TM7b enabled glucose transport by XylE and corresponding STD signals. Using complementary molecular dynamics simulations, together with structural, biochemical and STD NMR analysis of related parasitic and mammalian GLUTs, we identified TM7b as a key determinant of occluded state formation. We conclude that, rather than the initial substrate-binding event observed in experimental structures, formation of a substrate-induced transition-state intermediate is the primary determinant of specificity in transporters. PubMed: 41951885DOI: 10.1038/s41594-026-01784-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.42 Å) |
Structure validation
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