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Updated: Jun 27, 2026

Glutamine Flux Imaging Using Genetically Encoded Sensors
Published on: July 31, 2014
Structural analysis of human glutamine:fructose-6-phosphate amidotransferase, a key regulator in type 2 diabetes
Yuichiro Nakaishi1, Masahiko Bando, Hiroshi Shimizu
1Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co. Ltd., Kawauchi-cho, Tokushima, Japan. y_nakaishi@research.otsuka.co.jp
Abstract:
Glutamine:fructose-6-phosphate amidotransferase (GFAT) is a rate-limiting enzyme in the hexoamine biosynthetic pathway and plays an important role in type 2 diabetes. We now report the first structures of the isomerase domain of the human GFAT in the presence of cyclic glucose-6-phosphate and linear glucosamine-6-phosphate. The C-terminal tail including the active site displays a rigid conformation, similar to the corresponding Escherichia coli enzyme. The diversity of the CF helix near the active site suggests the helix is a major target for drug design. Our study provides insights into the development of therapeutic drugs for type 2 diabetes.
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