A 'specificity' pocket inferred from the crystal structures of the complexes of aldose reductase with the pharmaceutically important inhibitors tolrestat and sorbinil.
Urzhumtsev, A., Tete-Favier, F., Mitschler, A., Barbanton, J., Barth, P., Urzhumtseva, L., Biellmann, J.F., Podjarny, A., Moras, D.(1997) Structure 5: 601-612
- PubMed: 9195881 
- DOI: https://doi.org/10.1016/s0969-2126(97)00216-5
- Primary Citation of Related Structures:  
1AH0, 1AH3, 1AH4 - PubMed Abstract: 
Aldose reductase (AR) is an NADPH-dependent enzyme implicated in long-term diabetic complications. Buried at the bottom of a deep hydrophobic cleft, the NADPH coenzyme is surrounded by the conserved hydrophilic residues of the AR active site. The existence of an anionic binding site near the NADP+ has been determined from the structures of the complexes of AR with citrate, cacodylate and glucose-6-phosphate. The inhibitor zopolrestat binds to this anionic site, and in the hydrophobic cleft, after a change of conformation which opens a 'specificity' pocket.
Organizational Affiliation: 
UPR-de Biologie Structurale 9004 IGMBC CNRS/INSERM/ULP 1 rue Laurent Fries, B.P. 163, 67404, Illkirch, France.