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FEBS Lett. 2009 Jan 5;583(1):163-7. doi: 10.1016/j.febslet.2008.11.041. Epub 2008 Dec 6.

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

Author information

1
Medicinal 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.

PMID:
19059404
DOI:
10.1016/j.febslet.2008.11.041
[Indexed for MEDLINE]
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