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
-
Colloidal Supramolecular Aggregates for Therapeutic Application in Neuromedicine
Current Medicinal Chemistry Relationship Between Body Mass Index and Reproduction
Current Women`s Health Reviews Liver Disease in Diabetes Mellitus: Potential Therapeutic Value of Vitamin E-Silybin Phytosomal Complex
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Coumarin and Derivates as Lipid Lowering Agents
Current Topics in Medicinal Chemistry W-F Substitutions in Apomyoglobin Increase the Local Flexibility of the N-terminal Region Causing Amyloid Aggregation: A H/D Exchange Study
Protein & Peptide Letters Use of Human Umbilical Cord Blood (HUCB) Cells to Repair the Damaged Brain
Current Neurovascular Research Targeting Mitochondrial Oxidative Stress Through Lipoic Acid Synthase: A Novel Strategy to Manage Diabetic Cardiovascular Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry Neurodegeneration in the Brain Tumor Microenvironment: Glutamate in the Limelight
Current Neuropharmacology Cardiovascular Disease: What's All the AGE/RAGE About?
Cardiovascular & Hematological Disorders-Drug Targets Estrogen and Cytokines Production - The Possible Cause of Gender Differences in Neurological Diseases
Current Pharmaceutical Design Vitamin D Replacement and Type 2 Diabetes Mellitus
Current Diabetes Reviews The Role of Calcium Stores in Apoptosis and Autophagy
Current Molecular Medicine The Epidemiology of Cardiovascular Disease in Adults with Type 1 Diabetes
Current Diabetes Reviews Spinal Cord Injury Changes Cytokine Transport
CNS & Neurological Disorders - Drug Targets Therapeutic Potential of Cannabinoids in Neurodegenerative Disorders: A Selective Review
Current Pharmaceutical Design Manipulation of Microglial Activation as a Therapeutic Strategy in Alzheimers Disease
Current Medicinal Chemistry Signaling Pathways Involved in Physiopathology of Pancreatic β -Cells
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Pharmacological Manipulation of Neural Progenitor Pathways In Situ: Possibilities for Neural Restoration in the Injured Adult Brain
Current Medicinal Chemistry - Central Nervous System Agents Preface
Current Enzyme Inhibition Cannabinoids and Neuro-Inflammation: Regulation of Brain Immune Response
Recent Patents on CNS Drug Discovery (Discontinued)