Structural features of the aldose reductase and aldehyde reductase inhibitor-binding sites.
The three-dimensional structures of aldose reductase and aldehyde reductase, members of the aldo-keto reductase superfamily, are composed of similar alpha/beta TIM-barrels. However, examination of the structures reveals that the inhibitor-binding site of aldose reductase differs from that of aldehyde reductase due to the participation of non-conserved residues in its formation. This information will be useful in the design of inhibitors to prevent or delay diabetic retinopathy. A review of the structures of the inhibitor-binding sites is presented.
Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia. ossama.el-kabbani@vcp.monash.edu.au
O
O
El-Kabbani
D K
DK
Wilson
M
M
Petrash
F A
FA
Quiocho
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000201:enzymology; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
D004791:Enzyme Inhibitors; D000449:Aldehyde Reductase