4P9O: Complex Of Voltage-gated Ion Channel In A The Presence Of Channel Blocking Compound

Citation:
Abstract
Voltage-gated sodium channels are important targets for the development of pharmaceutical drugs, because mutations in different human sodium channel isoforms have causal relationships with a range of neurological and cardiovascular diseases. In this study, functional electrophysiological studies show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds and is inhibited by eukaryotic sodium channel blockers in a manner similar to the human Nav1.1 channel, despite millions of years of divergent evolution between the two types of channels. Crystal complexes of the NavMs pore with several brominated blocker compounds depict a common antagonist binding site in the cavity, adjacent to lipid-facing fenestrations proposed to be the portals for drug entry. In silico docking studies indicate the full extent of the blocker binding site, and electrophysiology studies of NavMs channels with mutations at adjacent residues validate the location. These results suggest that the NavMs channel can be a valuable tool for screening and rational design of human drugs.
PDB ID: 4P9ODownload
MMDB ID: 120506
PDB Deposition Date: 2014/4/4
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.89  Å
Source Organism:
Similar Structures:
Biological Unit for 4P9O: tetrameric; determined by author and by software (PISA)
Molecular Components in 4P9O
Label Count Molecule
Proteins (4 molecules)
4
Ion Transport Protein
Molecule annotation
Chemicals (10 molecules)
1
8
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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