4pa3: Difference between revisions
New page: '''Unreleased structure''' The entry 4pa3 is ON HOLD until Paper Publication Authors: Naylor, C.E., Bagneris, C., Wallace, B.A. Description: Structure of NavMS in complex with channel ... |
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==Structure of NavMS in complex with channel blocking compound== | |||
<StructureSection load='4pa3' size='340' side='right'caption='[[4pa3]], [[Resolution|resolution]] 3.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4pa3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Magnetococcus_marinus_MC-1 Magnetococcus marinus MC-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PA3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.25Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=2CV:HEGA-10'>2CV</scene>, <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4pa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pa3 OCA], [https://pdbe.org/4pa3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pa3 RCSB], [https://www.ebi.ac.uk/pdbsum/4pa3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pa3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0L5S6_MAGMM A0L5S6_MAGMM] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism.,Bagneris C, DeCaen PG, Naylor CE, Pryde DC, Nobeli I, Clapham DE, Wallace BA Proc Natl Acad Sci U S A. 2014 May 21. pii: 201406855. PMID:24850863<ref>PMID:24850863</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4pa3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ion channels 3D structures|Ion channels 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Magnetococcus marinus MC-1]] | |||
[[Category: Bagneris C]] | |||
[[Category: Naylor CE]] | |||
[[Category: Wallace BA]] | |||
Latest revision as of 10:13, 27 September 2023
Structural highlights
FunctionPublication Abstract from PubMedVoltage-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. Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism.,Bagneris C, DeCaen PG, Naylor CE, Pryde DC, Nobeli I, Clapham DE, Wallace BA Proc Natl Acad Sci U S A. 2014 May 21. pii: 201406855. PMID:24850863[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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