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Structural analysis of human glutamine:fructose‐6‐phosphate amidotransferase, a key regulator in type 2 diabetes
Author(s) -
Nakaishi Yuichiro,
Bando Masahiko,
Shimizu Hiroshi,
Watanabe Kenji,
Goto Fumitaka,
Tsuge Hideaki,
Kondo Kazumi,
Komatsu Makoto
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.11.041
Subject(s) - glutamine amidotransferase , glutamine , biochemistry , isomerase , enzyme , chemistry , regulator , amino acid , gene
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.