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Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT
by
Li, Chen
, Jiang, Daohua
, Chen, Ligong
, Wu, Di
, Xia, Zhanyi
, Chi, Cheng
, Wang, Yaqi
in
101/28
/ 101/58
/ 14/19
/ 631/45/535/1258/1259
/ 631/45/612/1237
/ 631/535
/ 631/57
/ 631/57/2283
/ 82/80
/ 82/83
/ Antiporters - antagonists & inhibitors
/ Antiporters - chemistry
/ Antiporters - genetics
/ Antiporters - metabolism
/ Biological Transport
/ Chlorogenic acid
/ Chromatography
/ Cryoelectron Microscopy
/ Drug development
/ Endoplasmic reticulum
/ Glucose
/ Glucose - metabolism
/ Glucose transporter
/ Glucose-6-phosphatase
/ Glucose-6-Phosphatase - genetics
/ Glucose-6-Phosphatase - metabolism
/ Glucose-6-phosphate
/ Glucose-6-Phosphate - chemistry
/ Glucose-6-Phosphate - metabolism
/ Glycogen
/ Glycogen Storage Disease Type I - genetics
/ Glycogen Storage Disease Type I - metabolism
/ Glycogens
/ HEK293 Cells
/ Homeostasis
/ Humanities and Social Sciences
/ Humans
/ Models, Molecular
/ Monosaccharide Transport Proteins - antagonists & inhibitors
/ Monosaccharide Transport Proteins - chemistry
/ Monosaccharide Transport Proteins - genetics
/ Monosaccharide Transport Proteins - metabolism
/ multidisciplinary
/ Phosphate transporter
/ Science
/ Science (multidisciplinary)
/ Storage diseases
/ Structure-function relationships
2025
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Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT
by
Li, Chen
, Jiang, Daohua
, Chen, Ligong
, Wu, Di
, Xia, Zhanyi
, Chi, Cheng
, Wang, Yaqi
in
101/28
/ 101/58
/ 14/19
/ 631/45/535/1258/1259
/ 631/45/612/1237
/ 631/535
/ 631/57
/ 631/57/2283
/ 82/80
/ 82/83
/ Antiporters - antagonists & inhibitors
/ Antiporters - chemistry
/ Antiporters - genetics
/ Antiporters - metabolism
/ Biological Transport
/ Chlorogenic acid
/ Chromatography
/ Cryoelectron Microscopy
/ Drug development
/ Endoplasmic reticulum
/ Glucose
/ Glucose - metabolism
/ Glucose transporter
/ Glucose-6-phosphatase
/ Glucose-6-Phosphatase - genetics
/ Glucose-6-Phosphatase - metabolism
/ Glucose-6-phosphate
/ Glucose-6-Phosphate - chemistry
/ Glucose-6-Phosphate - metabolism
/ Glycogen
/ Glycogen Storage Disease Type I - genetics
/ Glycogen Storage Disease Type I - metabolism
/ Glycogens
/ HEK293 Cells
/ Homeostasis
/ Humanities and Social Sciences
/ Humans
/ Models, Molecular
/ Monosaccharide Transport Proteins - antagonists & inhibitors
/ Monosaccharide Transport Proteins - chemistry
/ Monosaccharide Transport Proteins - genetics
/ Monosaccharide Transport Proteins - metabolism
/ multidisciplinary
/ Phosphate transporter
/ Science
/ Science (multidisciplinary)
/ Storage diseases
/ Structure-function relationships
2025
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Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT
by
Li, Chen
, Jiang, Daohua
, Chen, Ligong
, Wu, Di
, Xia, Zhanyi
, Chi, Cheng
, Wang, Yaqi
in
101/28
/ 101/58
/ 14/19
/ 631/45/535/1258/1259
/ 631/45/612/1237
/ 631/535
/ 631/57
/ 631/57/2283
/ 82/80
/ 82/83
/ Antiporters - antagonists & inhibitors
/ Antiporters - chemistry
/ Antiporters - genetics
/ Antiporters - metabolism
/ Biological Transport
/ Chlorogenic acid
/ Chromatography
/ Cryoelectron Microscopy
/ Drug development
/ Endoplasmic reticulum
/ Glucose
/ Glucose - metabolism
/ Glucose transporter
/ Glucose-6-phosphatase
/ Glucose-6-Phosphatase - genetics
/ Glucose-6-Phosphatase - metabolism
/ Glucose-6-phosphate
/ Glucose-6-Phosphate - chemistry
/ Glucose-6-Phosphate - metabolism
/ Glycogen
/ Glycogen Storage Disease Type I - genetics
/ Glycogen Storage Disease Type I - metabolism
/ Glycogens
/ HEK293 Cells
/ Homeostasis
/ Humanities and Social Sciences
/ Humans
/ Models, Molecular
/ Monosaccharide Transport Proteins - antagonists & inhibitors
/ Monosaccharide Transport Proteins - chemistry
/ Monosaccharide Transport Proteins - genetics
/ Monosaccharide Transport Proteins - metabolism
/ multidisciplinary
/ Phosphate transporter
/ Science
/ Science (multidisciplinary)
/ Storage diseases
/ Structure-function relationships
2025
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Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT
Journal Article
Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT
2025
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Overview
The human glucose-6-phosphate transporter (G6PT) moves glucose-6-phosphate (G6P) into the lumen of endoplasmic reticulum, playing a vital role in glucose homeostasis. Dysregulation of G6PT causes glycogen storage disease 1b. Despite its functional importance, the structure, G6P recognition, and inhibition mechanism of G6PT remain unclear. Here, we report the cryo-EM structures of human G6PT in apo, G6P-bound, and the specific inhibitor chlorogenic acid (CHA)-bound forms, elucidating the structural basis for G6PT transport and inhibition. The G6P pocket comprises subsite A for phosphate and subsite B for glucose. The CHA occupies the G6P site and locks G6PT in a partly-occluded state. Functional assays demonstrate that G6PT activity is enhanced by co-expression of glucose-6-phosphatase (G6PC), but G6PT does not form a complex with G6PC. Together, this study provides a solid foundation for understanding the structure‒function relationships and pathology of G6PT and sheds light on the future development of potential therapeutics targeting G6PT.
G6PT plays a vital role in glucose homeostasis by transporting glucose-6-phosphate to the lumen of ER. Here, authors present the cryo-EM structures of human G6PT in distinct forms, revealing the structural basis for transport and inhibition of G6PT.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 101/58
/ 14/19
/ 631/535
/ 631/57
/ 82/80
/ 82/83
/ Antiporters - antagonists & inhibitors
/ Glucose
/ Glucose-6-Phosphatase - genetics
/ Glucose-6-Phosphatase - metabolism
/ Glucose-6-Phosphate - chemistry
/ Glucose-6-Phosphate - metabolism
/ Glycogen
/ Glycogen Storage Disease Type I - genetics
/ Glycogen Storage Disease Type I - metabolism
/ Humanities and Social Sciences
/ Humans
/ Monosaccharide Transport Proteins - antagonists & inhibitors
/ Monosaccharide Transport Proteins - chemistry
/ Monosaccharide Transport Proteins - genetics
/ Monosaccharide Transport Proteins - metabolism
/ Science
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