4z91: Difference between revisions
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==ELIC cocrystallized with isofluorane in a desensitized state== | |||
<StructureSection load='4z91' size='340' side='right'caption='[[4z91]], [[Resolution|resolution]] 3.39Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4z91]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Dickeya_dadantii_3937 Dickeya dadantii 3937]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z91 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]] 3.3915Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4LE:(2R)-2-CHLORO-2-(DIFLUOROMETHOXY)-1,1,1-TRIFLUOROETHANE'>4LE</scene>, <scene name='pdbligand=4LJ:1.7.6+3-BROMANYLPROPAN-1-AMINE'>4LJ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=4z91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z91 OCA], [https://pdbe.org/4z91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z91 RCSB], [https://www.ebi.ac.uk/pdbsum/4z91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z91 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/E0SJQ4_DICD3 E0SJQ4_DICD3] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs. | |||
Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.,Chen Q, Kinde MN, Arjunan P, Wells MM, Cohen AE, Xu Y, Tang P Sci Rep. 2015 Sep 8;5:13833. doi: 10.1038/srep13833. PMID:26346220<ref>PMID:26346220</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4z91" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Dickeya dadantii 3937]] | ||
[[Category: Large Structures]] | |||
[[Category: Arjunan P]] | |||
[[Category: Chen Q]] | |||
[[Category: Cohen A]] | |||
[[Category: Kinde MN]] | |||
[[Category: Tang P]] | |||
[[Category: Xu Y]] | |||
Latest revision as of 11:14, 27 September 2023
ELIC cocrystallized with isofluorane in a desensitized stateELIC cocrystallized with isofluorane in a desensitized state
Structural highlights
FunctionPublication Abstract from PubMedPentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs. Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.,Chen Q, Kinde MN, Arjunan P, Wells MM, Cohen AE, Xu Y, Tang P Sci Rep. 2015 Sep 8;5:13833. doi: 10.1038/srep13833. PMID:26346220[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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