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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

[ Vol. 15 , Issue. 8 ]

Author(s):

Rithvik S. Vinekar and Ramanathan Sowdhamini*   Pages 1062 - 1072 ( 11 )

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.

Affiliation:

National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore, National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore

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