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PDBsum entry 4yb9
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Transport protein
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PDB id
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4yb9
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References listed in PDB file
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Key reference
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Title
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Structure and mechanism of the mammalian fructose transporter glut5.
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Authors
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N.Nomura,
G.Verdon,
H.J.Kang,
T.Shimamura,
Y.Nomura,
Y.Sonoda,
S.A.Hussien,
A.A.Qureshi,
M.Coincon,
Y.Sato,
H.Abe,
Y.Nakada-Nakura,
T.Hino,
T.Arakawa,
O.Kusano-Arai,
H.Iwanari,
T.Murata,
T.Kobayashi,
T.Hamakubo,
M.Kasahara,
S.Iwata,
D.Drew.
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Ref.
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Nature, 2015,
526,
397-401.
[DOI no: ]
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PubMed id
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Abstract
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The altered activity of the fructose transporter GLUT5, an isoform of the
facilitated-diffusion glucose transporter family, has been linked to disorders
such as type 2 diabetes and obesity. GLUT5 is also overexpressed in certain
tumour cells, and inhibitors are potential drugs for these conditions. Here we
describe the crystal structures of GLUT5 from Rattus norvegicus and Bos taurus
in open outward- and open inward-facing conformations, respectively. GLUT5 has a
major facilitator superfamily fold like other homologous monosaccharide
transporters. On the basis of a comparison of the inward-facing structures of
GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single
point mutation is enough to switch the substrate-binding preference of GLUT5
from fructose to glucose. A comparison of the substrate-free structures of GLUT5
with occluded substrate-bound structures of Escherichia coli XylE suggests that,
in addition to 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 in such monosaccharide
transporters.
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