Abstract
X-ray crystallography, structural bioinformatics and computational chemistry have become important techniques in the discovery and development of effective and safe new drugs. From a drug discovery point of view, membrane proteins are among the most interesting molecular targets, but the current knowledge about detailed 3D structures of membrane proteins is sparse. Homology modeling techniques may provide structural knowledge about membrane proteins and their interactions with drugs and other molecules. The neurotransmitter sodium symporters (NSS) are the molecular targets of many pharmacologically active substances, and we have used three different secondary transporters as templates for modeling the NSS proteins DAT, NET and SERT. The first template was based on the electron density projection map of the Escherichia coli Na+/H+ antiporter (NhaA), while later the X-ray structure of Lac Permease (symporter) was used as a template. The helical architectures of these templates have a lot in common, and models based on both could contribute with structural explanations of several experimental studies in spite of low homology with NSS proteins. In 2005 the crystal structure of a bacterial homologue of the human monoamine neurotransmitter transporter Aquifex aeolicus (LeuTAa) was reported. This structure was the first experimental structure of a NSS family member, and represented a breakthrough for homology modeling of pharmacological important NSS proteins. Since then several X-ray structures LeuTAa in complex with pharmacologically important compounds have been published. Homology models of NSS proteins, combined with site-directed mutagenesis data, have identified ligand binding sites and contributed with important knowledge for new drug development.
Keywords: 3-Dimensional structure, dopamine transporter, drug interactions, molecular structure, molecular mechanisms, monoamine transporters, noradrenaline transporter, serotonin transporter, NSS proteins, structural bioinformatics
Current Medicinal Chemistry
Title: Templates and Models of Monoamine Transporter Proteins
Volume: 18 Issue: 30
Author(s): I. Sylte, A.W. Ravna and S.G. Dahl
Affiliation:
Keywords: 3-Dimensional structure, dopamine transporter, drug interactions, molecular structure, molecular mechanisms, monoamine transporters, noradrenaline transporter, serotonin transporter, NSS proteins, structural bioinformatics
Abstract: X-ray crystallography, structural bioinformatics and computational chemistry have become important techniques in the discovery and development of effective and safe new drugs. From a drug discovery point of view, membrane proteins are among the most interesting molecular targets, but the current knowledge about detailed 3D structures of membrane proteins is sparse. Homology modeling techniques may provide structural knowledge about membrane proteins and their interactions with drugs and other molecules. The neurotransmitter sodium symporters (NSS) are the molecular targets of many pharmacologically active substances, and we have used three different secondary transporters as templates for modeling the NSS proteins DAT, NET and SERT. The first template was based on the electron density projection map of the Escherichia coli Na+/H+ antiporter (NhaA), while later the X-ray structure of Lac Permease (symporter) was used as a template. The helical architectures of these templates have a lot in common, and models based on both could contribute with structural explanations of several experimental studies in spite of low homology with NSS proteins. In 2005 the crystal structure of a bacterial homologue of the human monoamine neurotransmitter transporter Aquifex aeolicus (LeuTAa) was reported. This structure was the first experimental structure of a NSS family member, and represented a breakthrough for homology modeling of pharmacological important NSS proteins. Since then several X-ray structures LeuTAa in complex with pharmacologically important compounds have been published. Homology models of NSS proteins, combined with site-directed mutagenesis data, have identified ligand binding sites and contributed with important knowledge for new drug development.
Export Options
About this article
Cite this article as:
Sylte I., Ravna A.W. and Dahl S.G., Templates and Models of Monoamine Transporter Proteins, Current Medicinal Chemistry 2011; 18 (30) . https://dx.doi.org/10.2174/092986711797379203
DOI https://dx.doi.org/10.2174/092986711797379203 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Metal Nanocomposites Based Electrochemical Sensor Platform for Few
Emerging Biomarkers
Current Analytical Chemistry Neuropeptides as Therapeutic Targets in Anxiety Disorders
Current Pharmaceutical Design Novel Therapeutic Approaches to Autoimmune Demyelinating Disorders
Current Pharmaceutical Design Persistent Psychosis from Toluene Exposure; More Likely Coincidence than Cause: A Review of our Experience and the Literature
Current Psychiatry Reviews Vaccine Therapy Update for Pregnant, Immunocompromised, and Chronic Diseases Patients
Recent Patents on Inflammation & Allergy Drug Discovery Retracted: Junk Food Consumption, Perceptions and Associated Factors among the Private School Children
Current Nutrition & Food Science Therapeutic Approaches for Dominant Muscle Diseases: Highlight on Myotonic Dystrophy
Current Gene Therapy Cognitive Behavioral Therapy for Psychosis Prevention and Treatment in Youth
Current Psychiatry Reviews Molecular Self-Assembly of Peptide Nanostructures: Mechanism of Association and Potential Uses
Current Nanoscience Cytokines in Neuroinflammation and Alzheimers Disease
Current Drug Targets The Role of Placental Carbonyl Reducing Enzymes in Biotransformation of Bupropion and 4-methylnitrosamino-1-(3-pyridyl)-1-butanone
Drug Metabolism Letters Targeting Mitogen-Activated Protein Kinase Phosphatase-1 (MKP-1): Structure-Based Design of MKP-1 Inhibitors and Upregulators
Current Medicinal Chemistry Synthesis and Antitumor Evaluation of Novel N-substituted Norcantharidin Imidazolium Derivatives
Current Organic Synthesis Temporal Expression of Mutant TDP-43 Correlates with Early Amyotrophic Lateral Sclerosis Phenotype and Motor Weakness
Current Neurovascular Research Application of In Vivo Animal Models to Characterize the Pharmacokinetic and Pharmacodynamic Properties of Drug Candidates in Discovery Settings
Combinatorial Chemistry & High Throughput Screening Neurotrophic Factors - A Tool for Therapeutic Strategies in Neurological,Neuropsychiatric and Neuroimmunological Diseases?
Current Medicinal Chemistry Medicinal Properties of the Jamaican Pepper Plant Pimenta dioica and Allspice
Current Drug Targets Method Validation for the Determination of Carbamazepine in Spiked-saliva Using HPLC-UV for Therapeutic Drug Monitoring Application
Current Psychopharmacology Cerebral Microbleeds Do Not Predict Hemorrhagic Transformation in Acute Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease
Current Neurovascular Research A Liquid–Liquid Extraction–Assisted HPLC Procedure for Assaying of Citalopram in Depressed Women Saliva
Current Pharmaceutical Analysis