Structural analysis of human glutamine:fructose‐6‐phosphate amidotransferase, a key regulator in type 2 diabetes

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.