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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A Critical and Comprehensive Insight on Heme Oxygenase and Related Products Including Carbon Monoxide, Bilirubin, Biliverdin and Ferritin in Type-1 and Type-2 Diabetes
Current Pharmaceutical Design Novel S-Nitrosothiols Have Potential Therapeutic Uses for Cystic Fibrosis
Current Pharmaceutical Design Mitochondrial Disturbances, Tryptophan Metabolites and Neurodegeneration: Medicinal Chemistry Aspects
Current Medicinal Chemistry Management of Type-1 and Type-2 Diabetes by Insulin Injections in Diabetology Clinics - A Scientific Research Review
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Management of Exercise-induced Glycemic Imbalances in Type 1 Diabetes
Current Diabetes Reviews Antisynthetase Syndrome: A Review of Etiopathogenesis, Diagnosis and Management
Current Medicinal Chemistry Aldose Reductase in the Retina
Current Enzyme Inhibition Symptomatic Improvement, Increased Life-Span and Sustained Cell Homing in Amyotrophic Lateral Sclerosis After Transplantation of Human Umbilical Cord Blood Cells Genetically Modified with Adeno-Viral Vectors Expressing a Neuro-Protective Factor and a Neural Cell Adhesion Molecule
Current Gene Therapy Obstructive Sleep Apnoea Syndrome and Diabetes. Fortuitous Association or Interaction?
Current Diabetes Reviews Targeting Microglial Activation in Stroke Therapy: Pharmacological Tools and Gender Effects
Current Medicinal Chemistry Patents Relating to the Application of Autologous Bone Marrow-Derived Mesenchymal Stromal Cell and Whole Marrow Transplantation for Neurodegenerative Diseases: A Review
Recent Patents on Regenerative Medicine Gliclazide, Inflammation and Atherosclerosis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Role of Thrombin Activatable Fibrinolysis Inhibitor in Endocrine and Cardiovascular Disorders: An Update
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery The Endocannabinoid System in Amyotrophic Lateral Sclerosis
Current Pharmaceutical Design Targeting Neurotrophin Receptors in the Central Nervous System
CNS & Neurological Disorders - Drug Targets The Anti-Oxidant Properties of Isothiocyanates: A Review
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Diabetic Retinopathy, Superoxide Damage and Antioxidants
Current Pharmaceutical Biotechnology Cardiovascular Effects of Liraglutide
Current Hypertension Reviews Protein Aggregation in Alzheimers Disease and Other Neoropathological Disorders
Current Alzheimer Research Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Clinical Update of Safety and Efficacy
Current Diabetes Reviews