Abstract
Background: The eukaryotic voltage-gated sodium channel(e-Nav) is a large asymmetric transmembrane protein with important functions concerning neurological function. No structure has been resolved at high resolution for this protein.
Methods: A homology model of the transmembrane and extracellular regions of an Anopheles gambiae para-like channel with emphasis on the pore entrance has been constructed, based upon the templates provided by a prokaryotic sodium channel and a potassium two-pore channel. The latter provides a template for the extracellular regions, which are located above the entrance to the pore, which is likely to open at a side of a dome formed by these loops.
Results: A model created with this arrangement shows a structure similar to low-resolution cryoelectron microscope images of a related structure. The pore entrance also shows favorable electrostatic interface.
Conclusion: Residues responsible for the negative charge around the pore have been traced in phylogeny to highlight their importance. This model is intended for the study of pore-blocking toxins.
Keywords: Eukaryotic voltage gated sodium channel, homology model, pore blocker, toxin, extracellular interface, transmembrane, anopheles.
Graphical Abstract
Current Neuropharmacology
Title:Three-dimensional Modelling of the Voltage-gated Sodium Ion Channel from Anopheles gambiae Reveals Spatial Clustering of Evolutionarily Conserved Acidic Residues at the Extracellular Sites
Volume: 15 Issue: 8
Author(s): Rithvik S. Vinekar and Ramanathan Sowdhamini*
Affiliation:
- National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore,India
Keywords: Eukaryotic voltage gated sodium channel, homology model, pore blocker, toxin, extracellular interface, transmembrane, anopheles.
Abstract: Background: The eukaryotic voltage-gated sodium channel(e-Nav) is a large asymmetric transmembrane protein with important functions concerning neurological function. No structure has been resolved at high resolution for this protein.
Methods: A homology model of the transmembrane and extracellular regions of an Anopheles gambiae para-like channel with emphasis on the pore entrance has been constructed, based upon the templates provided by a prokaryotic sodium channel and a potassium two-pore channel. The latter provides a template for the extracellular regions, which are located above the entrance to the pore, which is likely to open at a side of a dome formed by these loops.
Results: A model created with this arrangement shows a structure similar to low-resolution cryoelectron microscope images of a related structure. The pore entrance also shows favorable electrostatic interface.
Conclusion: Residues responsible for the negative charge around the pore have been traced in phylogeny to highlight their importance. This model is intended for the study of pore-blocking toxins.
Export Options
About this article
Cite this article as:
Vinekar S. Rithvik and Sowdhamini Ramanathan*, Three-dimensional Modelling of the Voltage-gated Sodium Ion Channel from Anopheles gambiae Reveals Spatial Clustering of Evolutionarily Conserved Acidic Residues at the Extracellular Sites, Current Neuropharmacology 2017; 15 (8) . https://dx.doi.org/10.2174/1567201814666161205131213
DOI https://dx.doi.org/10.2174/1567201814666161205131213 |
Print ISSN 1570-159X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6190 |
- 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
- Forthcoming Thematic Issues
Related Articles
-
Primary and Secondary Insomnia: Prevalence, Causes and Current Therapeutics
Current Medicinal Chemistry - Central Nervous System Agents Dynamic Expression of MicroRNAs (183, 135a, 125b, 128, 30c and 27a) in the Rat Pilocarpine Model and Temporal Lobe Epilepsy Patients
CNS & Neurological Disorders - Drug Targets In Vitro Skin Permeation Enhancement of Sumatriptan by Microneedle Application
Current Drug Delivery Allosteric Modulators for Adenosine Receptors: An Alternative to the Orthosteric Ligands
Current Topics in Medicinal Chemistry Psychiatric Disorders Associated with FXTAS
Current Psychiatry Reviews 3D QSAR Studies on 1, 3, 4-Thiadiazole Derivatives: An Approach to Design Novel Anticonvulsants
Medicinal Chemistry Improving Cognitive Outcome in Cerebral Malaria: Insights from Clinical and Experimental Research
Central Nervous System Agents in Medicinal Chemistry α-Melanocyte Stimulating Hormone as a Potential Therapy for Alzheimer's Disease
Current Alzheimer Research Blockers of Voltage-Gated Sodium Channels for the Treatment of Central Nervous System Diseases
Recent Patents on CNS Drug Discovery (Discontinued) In Search of Novel and Therapeutically Significant Melatoninergic Ligands
Recent Patents on CNS Drug Discovery (Discontinued) Targeting the Brain: Advances in Drug Delivery
Current Pharmaceutical Biotechnology Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Kernel-Based Feature Selection Techniques for Transport Proteins Based on Star Graph Topological Indices
Current Topics in Medicinal Chemistry An Overview of Galenic Preparation Methods for Medicinal Cannabis
Current Bioactive Compounds Microendophenotypes of Psychiatric Disorders: Phenotypes of Psychiatric Disorders at the Level of Molecular Dynamics, Synapses, Neurons, and Neural Circuits
Current Molecular Medicine Examination of Hippocampal Differences Between Alzheimer Disease, Amnestic Mild Cognitive Impairment and Normal Aging: Diffusion Kurtosis
Current Alzheimer Research Cofilin Rod Formation in Neurons Impairs Neuronal Structure and Function
CNS & Neurological Disorders - Drug Targets Suicidality and Cannabidiol: Opportunities and Challenges
Current Neuropharmacology Possible Protecting Role of TNF-α in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NFκB Signaling Pathway
Current Alzheimer Research FTY720 (Fingolimod) Ameliorates Brain Injury through Multiple Mechanisms and is a Strong Candidate for Stroke Treatment
Current Medicinal Chemistry