Sun, L; Zeng, Xin; Yan, C; Sun, X; Gong, X; Rao, Yu; Yan, N
Gl°Cose transporters are essential for metabolism of gl°Cose in cells of diverse organisms from microbes to humans, exemplified by the disease-related human proteins GLUT1, 2, 3 and 4. Despite rigorous efforts, the str°Ctural information for GLUT1-4 or their homologues remains largely unknown. Here we report three related crystal str°Ctures of XylE, an Escherichia coli homologue of GLUT1-4, in complex with D-xylose, D-gl°Cose and 6-bromo-6-deoxy-D-gl°Cose, at resolutions of 2.8, 2.9 and 2.6Å , respectively. The str°Cture consists of a typical major facilitator superfamily fold of 12 transmembrane segments and a unique intracellular four-helix domain. XylE was captured in an outward-facing, partly occludedconformation.Mostof the important amino acids responsible for recognitionof D-xylose or D-gl°Cose are invariant in GLUT1-4, suggesting functional andmechanistic conservations. Str°Cture-based modelling of GLUT1-4 allows mapping and interpretation of disease-related mutations. The str°Ctural and biochemical information reported here constitutes an important framework for mechanistic understanding of gl°Cose transporters and sugar porters in general. [PUBLICATION ABSTRACT] Glucose transporters are essential for metabolism of glucose in cells of diverse organisms from microbes to humans, exemplified by the disease-related human proteins GLUT1, 2, 3 and 4. Despite rigorous efforts, the structural information for GLUT1-4 or their homologues remains largely unknown. Here we report three related crystal structures of XylE, an Escherichia coli homologue of GLUT1-4, in complex with d-xylose, d-glucose and 6-bromo-6-deoxy-D-glucose, at resolutions of 2.8, 2.9 and 2.6Å, respectively. The structure consists of a typical major facilitator superfamily fold of 12 transmembrane segments and a unique intracellular four-helix domain. XylE was captured in an outward-facing, partly occluded conformation. Most of the important amino acids responsible for recognition of D-xylose or d-glucose are invariant in GLUT1-4, suggesting functional and mechanistic conservations. Structure-based modelling of GLUT1-4 allows mapping and interpretation of disease-related mutations. The structural and biochemical information reported here constitutes an important framework for mechanistic understanding of glucose transporters and sugar porters in general.
Hydrogen Bonding; Biological Transport; Glucose Transporter Type 1; E coli; Structure-Activity Relationship; Xylose; Escherichia coli Proteins; Deoxyglucose; Humans; Models, Molecular; Ligands; Substrate Specificity; Protein Conformation; Mutation; Glucose Transport Proteins, Facilitative; Structural Homology, Protein; Proteins; Crystallography, X-Ray; Symporters; Glucose; 2012)