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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore, India.
authors.forename: Rithvik S
authors.initials: RS
authors.lastname: Vinekar
authors.affiliation: National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore, India.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Sowdhamini
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000737:chemistry*; D001665:Binding Sites / Q000502:physiology; D005075:Biological Evolution; D001703:Biophysics; D003198:Computer Simulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D010802:Phylogeny; D015222:Sodium Channels / Q000737:chemistry* / Q000502:physiology
chemical_list: D015222:Sodium Channels
keywords: Eukaryotic voltage gated sodium channel; anopheles.; extracellular interface; homology model; pore blocker; toxin; transmembrane