Rithvik S. Vinekar and Ramanathan Sowdhamini* Pages 1062 - 1072 ( 11 )
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.
Eukaryotic voltage gated sodium channel, homology model, pore blocker, toxin, extracellular interface, transmembrane, anopheles.
National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore, National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore