title: Crystal structure of a glucose/H+ symporter and its mechanism of action.
abstract: Glucose transporters are required to bring glucose into cells, where it is an essential energy source and precursor in protein and lipid synthesis. These transporters are involved in important common diseases such as cancer and diabetes. Here, we report the crystal structure of the Staphylococcus epidermidis glucose/H(+) symporter in an inward-facing conformation at 3.2-Å resolution. The Staphylococcus epidermidis glucose/H(+) symporter is homologous to human glucose transporters, is very specific and has high avidity for glucose, and is inhibited by the human glucose transport inhibitors cytochalasin B, phloretin, and forskolin. On the basis of the crystal structure in conjunction with mutagenesis and functional studies, we propose a mechanism for glucose/H(+) symport and discuss the symport mechanism versus facilitated diffusion.
authors.affiliation: Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, IL 60064.
authors.forename: Cristina V
authors.initials: CV
authors.lastname: Iancu
authors.forename: Jamillah
authors.initials: J
authors.lastname: Zamoon
authors.forename: Sang Bum
authors.initials: SB
authors.lastname: Woo
authors.forename: Alexander
authors.initials: A
authors.lastname: Aleshin
authors.forename: Jun-yong
authors.initials: JY
authors.lastname: Choe
mesh_terms: D001692:Biological Transport / Q000502:physiology; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D003460:Crystallization; D003571:Cytochalasin B / Q000494:pharmacology; D004926:Escherichia coli; D051246:Glucose Transport Proteins, Facilitative / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D010693:Phloretin / Q000494:pharmacology; D011487:Protein Conformation; D017385:Sequence Homology; D013212:Staphylococcus epidermidis / Q000737:chemistry* / Q000235:genetics
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D005576:Colforsin; D003571:Cytochalasin B; D010693:Phloretin
keywords: GLUT; major facilitator superfamily; membrane protein; solute-carrier 2A; sugar transporter