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PDBsum entry 4zwc
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Transport protein
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PDB id
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4zwc
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References listed in PDB file
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Key reference
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Title
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Molecular basis of ligand recognition and transport by glucose transporters.
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Authors
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D.Deng,
P.Sun,
C.Yan,
M.Ke,
X.Jiang,
L.Xiong,
W.Ren,
K.Hirata,
M.Yamamoto,
S.Fan,
N.Yan.
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Ref.
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Nature, 2015,
526,
391-396.
[DOI no: ]
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PubMed id
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Abstract
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The major facilitator superfamily glucose transporters, exemplified by human
GLUT1-4, have been central to the study of solute transport. Using lipidic cubic
phase crystallization and microfocus X-ray diffraction, we determined the
structure of human GLUT3 in complex with D-glucose at 1.5 Å resolution in an
outward-occluded conformation. The high-resolution structure allows
discrimination of both α- and β-anomers of D-glucose. Two additional
structures of GLUT3 bound to the exofacial inhibitor maltose were obtained at
2.6 Å in the outward-open and 2.4 Å in the outward-occluded states. In all
three structures, the ligands are predominantly coordinated by polar residues
from the carboxy terminal domain. Conformational transition from outward-open to
outward-occluded entails a prominent local rearrangement of the extracellular
part of transmembrane segment TM7. Comparison of the outward-facing GLUT3
structures with the inward-open GLUT1 provides insights into the alternating
access cycle for GLUTs, whereby the C-terminal domain provides the primary
substrate-binding site and the amino-terminal domain undergoes rigid-body
rotation with respect to the C-terminal domain. Our studies provide an important
framework for the mechanistic and kinetic understanding of GLUTs and shed light
on structure-guided ligand design.
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