4CBC
Open-form NavMS Sodium Channel Pore (with C-terminal Domain) after thallium soak
Summary for 4CBC
| Entry DOI | 10.2210/pdb4cbc/pdb |
| Related | 4CAL 4CBD |
| Descriptor | ION TRANSPORT PROTEIN, HEGA-10, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | transport protein, sodium channel, selectivity filter, membrane protein |
| Biological source | MAGNETOCOCCUS MARINUS MC-1 |
| Total number of polymer chains | 4 |
| Total formula weight | 69760.88 |
| Authors | Bagneris, C.,Naylor, C.E.,Wallace, B.A. (deposition date: 2013-10-12, release date: 2014-05-28, Last modification date: 2023-12-20) |
| Primary citation | Bagneris, C.,Decaen, P.G.,Naylor, C.E.,Pryde, D.C.,Nobeli, I.,Clapham, D.E.,Wallace, B.A. Prokaryotic Navms Channel as a Structural and Functional Model for Eukaryotic Sodium Channel Antagonism. Proc.Natl.Acad.Sci.USA, 111:8428-, 2014 Cited by PubMed 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. PubMed: 24850863DOI: 10.1073/PNAS.1406855111 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.664 Å) |
Structure validation
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