4xdk: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4xdk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XDK FirstGlance]. <br> | <table><tr><td colspan='2'>[[4xdk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XDK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=405:(3S)-3-PHENYL-3-[4-(TRIFLUOROMETHYL)PHENOXY]PROPAN-1-AMINE'>405</scene>, <scene name='pdbligand=408:(3R)-3-PHENYL-3-[4-(TRIFLUOROMETHYL)PHENOXY]PROPAN-1-AMINE'>408</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.6Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=405:(3S)-3-PHENYL-3-[4-(TRIFLUOROMETHYL)PHENOXY]PROPAN-1-AMINE'>405</scene>, <scene name='pdbligand=408:(3R)-3-PHENYL-3-[4-(TRIFLUOROMETHYL)PHENOXY]PROPAN-1-AMINE'>408</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</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=4xdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdk OCA], [https://pdbe.org/4xdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xdk RCSB], [https://www.ebi.ac.uk/pdbsum/4xdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xdk ProSAT]</span></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=4xdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdk OCA], [https://pdbe.org/4xdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xdk RCSB], [https://www.ebi.ac.uk/pdbsum/4xdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xdk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 13:48, 10 January 2024
Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1) in complex with norfluoxetineCrystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1) in complex with norfluoxetine
Structural highlights
FunctionKCNKA_HUMAN Outward rectifying potassium channel. Produces rapidly activating and non-inactivating outward rectifier K(+) currents. Activated by arachidonic acid and other naturally occurring unsaturated free fatty acids. Publication Abstract from PubMedTREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac. K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.,Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S, Ruda GF, Clausen MV, Cao L, Brennan PE, Burgess-Brown NA, Sansom MS, Tucker SJ, Carpenter EP Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512. PMID:25766236[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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