Abstract
Sorbitol dehydrogenase (SDH), a member of the medium-chain dehydrogenase / reductase protein family and the second enzyme of the polyol pathway of glucose metabolism, converts sorbitol to fructose strictly using NAD+ as coenzyme. SDH is expressed almost ubiquitously in all mammalian tissues. The enzyme has attracted considerable interest due to its implication in the development of diabetic complications and thus its tertiary structure may facilitate the development of drugs for the treatment of diabetes sufferers. Modelling studies suggest that SDH is structurally homologous to mammalian alcohol dehydrogenase with respect to conserved zinc binding motif and a hydrophobic substrate-binding pocket. Recently, the three-dimensional (3- D) structure of a mammalian SDH was solved, and it was found that while the overall 3-D structures of SDH and alcohol dehydrogenase are similar, the zinc coordination in the active sites of the two enzymes is different. The available structural and biochemical information of SDH are currently being utilized in a structure-based approach to develop drugs for the treatment or prevention of the complications of diabetes. This review provides an overview of the recent advances in the structure, function and drug development fields of sorbitol dehydrogenase.
Keywords: sorbitol dehydrogenase, structure, function, inhibitors, ligand design
Current Medicinal Chemistry
Title: Sorbitol Dehydrogenase: Structure, Function and Ligand Design
Volume: 11 Issue: 4
Author(s): O. El-Kabbani, C. Darmanin and R. P.-T. Chung
Affiliation:
Keywords: sorbitol dehydrogenase, structure, function, inhibitors, ligand design
Abstract: Sorbitol dehydrogenase (SDH), a member of the medium-chain dehydrogenase / reductase protein family and the second enzyme of the polyol pathway of glucose metabolism, converts sorbitol to fructose strictly using NAD+ as coenzyme. SDH is expressed almost ubiquitously in all mammalian tissues. The enzyme has attracted considerable interest due to its implication in the development of diabetic complications and thus its tertiary structure may facilitate the development of drugs for the treatment of diabetes sufferers. Modelling studies suggest that SDH is structurally homologous to mammalian alcohol dehydrogenase with respect to conserved zinc binding motif and a hydrophobic substrate-binding pocket. Recently, the three-dimensional (3- D) structure of a mammalian SDH was solved, and it was found that while the overall 3-D structures of SDH and alcohol dehydrogenase are similar, the zinc coordination in the active sites of the two enzymes is different. The available structural and biochemical information of SDH are currently being utilized in a structure-based approach to develop drugs for the treatment or prevention of the complications of diabetes. This review provides an overview of the recent advances in the structure, function and drug development fields of sorbitol dehydrogenase.
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Cite this article as:
El-Kabbani O., Darmanin C. and Chung P.-T. R., Sorbitol Dehydrogenase: Structure, Function and Ligand Design, Current Medicinal Chemistry 2004; 11 (4) . https://dx.doi.org/10.2174/0929867043455927
DOI https://dx.doi.org/10.2174/0929867043455927 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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