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
| Autor: | Ramanathan Sowdhamini, Rithvik S. Vinekar |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine Anopheles gambiae Amino Acid Motifs Neurological function Biophysics Article Sodium Channels 03 medical and health sciences pore blocker 0302 clinical medicine Anopheles Extracellular Animals Humans Computer Simulation Pharmacology (medical) homology model Amino Acid Sequence Homology modeling toxin Phylogeny Pharmacology Binding Sites biology Voltage-gated ion channel extracellular interface Ecology Sodium channel Eukaryotic voltage gated sodium channel General Medicine Hydrogen-Ion Concentration biology.organism_classification Biological Evolution Transmembrane protein transmembrane Psychiatry and Mental health 030104 developmental biology Neurology Spatial clustering Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Current Neuropharmacology |
| ISSN: | 1570-159X |
| DOI: | 10.2174/1567201814666161205131213 |
| Popis: | 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 cryo-electron 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.. |
| Databáze: | OpenAIRE |
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