2.A.1.1.13
Fructose uniporter, GLUT5.  The proteins from rat and cow have been crystalized and their structures have been determined in the open outward- and open inward-facing conformations, respectively. On the basis of comparisons of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, a single point mutation proved to be enough to switch the substrate-binding preference from fructose to glucose. A comparison of the substrate-free structures of GLUT5 with occluded substrate-bound structures of E. coli XylE suggested that, in addition to a global rocker-switch-like re-orientation of the bundles, local asymmetric rearrangements of carboxy-terminal transmembrane bundle helices, TM7 and TM10, underlie a 'gated-pore' transport mechanism (Nomura et al. 2015).  GLUT5 is preferentially used for fructose uptake under (near) anoxic glycolysis to avoid feedback inhibition of phosphofructokinase (Park et al. 2017). Residues involved in fructose recognition have been identified (Ebert et al. 2017). Glucose (Glut-1 and 3) and fructose (Glut-2 and 5) transporter expression and regulation in the hummingbird occur independently of each other (Ali et al. 2020). Complex plastic mechanisms allow adaptation to environmental changes (Huang et al. 2023). C-3 modified 2,5-anhydromannitol (2,5-AM) compounds are inhibitory D-fructose analogues (Rana et al. 2023).  Discrimination of GLUTs by fructose isomers enables simultaneous screening of GLUT5 and GLUT2 activities in live cells (Gora et al. 2023). It may play a role in tumorigenesis (Hadzi-Petrushev et al. 2024).