Download MendeleyStructural analysis of human glutamine:fructose-6-phosphate amidotransferase, a key regulator in type 2 diabetes
Nakaishi, Y., Bando, M., Shimizu, H., Watanabe, K., Goto, F., Tsuge, H., Kondo, K., Komatsu, M.(2009) FEBS Lett 583: 163-167
- PubMed: 19059404
- DOI: https://doi.org/10.1016/j.febslet.2008.11.041
- Primary Citation of Related Structures:
2ZJ3, 2ZJ4 - PubMed 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.
Organizational Affiliation:
Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co. Ltd., Kawauchi-cho, Tokushima, Japan. [email protected]
