2hjf: Difference between revisions
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< | ==Potassium channel kcsa-fab complex with tetrabutylammonium (TBA)== | ||
<StructureSection load='2hjf' size='340' side='right'caption='[[2hjf]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2hjf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HJF 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]] 2.9Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TBA:TETRABUTYLAMMONIUM+ION'>TBA</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=2hjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hjf OCA], [https://pdbe.org/2hjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hjf RCSB], [https://www.ebi.ac.uk/pdbsum/2hjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hjf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KCSA_STRLI KCSA_STRLI] Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+).<ref>PMID:7489706</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hj/2hjf_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hjf ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The mechanism of intracellular blockade of the KcsA potassium channel by tetrabutylammonium (TBA) is investigated through functional, structural and computational studies. Using planar-membrane electrophysiological recordings, we characterize the binding kinetics as well as the dependence on the transmembrane voltage and the concentration of the blocker. It is found that the apparent affinity of the complex is significantly greater than that of any of the eukaryotic K(+) channels studied previously, and that the off-rate increases with the applied transmembrane voltage. In addition, we report a crystal structure of the KcsA-TBA complex at 2.9 A resolution, with TBA bound inside the large hydrophobic cavity located at the center of the channel, consistent with the results of previous functional and structural studies. Of particular interest is the observation that the presence of TBA has a negligible effect on the channel structure and on the position of the potassium ions occupying the selectivity filter. Inspection of the electron density corresponding to TBA suggests that the ligand may adopt more than one conformation in the complex, though the moderate resolution of the data precludes a definitive interpretation on the basis of the crystallographic refinement methods alone. To provide a rationale for these observations, we carry out an extensive conformational sampling of an atomic model of TBA bound in the central cavity of KcsA, using the Hamiltonian replica-exchange molecular dynamics simulation method. Comparison of the simulated and experimental density maps indicates that the latter does reflect at least two distinct binding orientations of TBA. The simulations show also that the relative population of these binding modes is dependent on the ion configuration occupying the selectivity filter, thus providing a clue to the nature of the voltage-dependence of the binding kinetics. | |||
Mechanism of intracellular block of the KcsA K+ channel by tetrabutylammonium: insights from X-ray crystallography, electrophysiology and replica-exchange molecular dynamics simulations.,Faraldo-Gomez JD, Kutluay E, Jogini V, Zhao Y, Heginbotham L, Roux B J Mol Biol. 2007 Jan 19;365(3):649-62. Epub 2006 Sep 29. PMID:17070844<ref>PMID:17070844</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2hjf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
== | |||
< | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Streptomyces lividans]] | [[Category: Streptomyces lividans]] | ||
[[Category: Faraldo-Gomez | [[Category: Faraldo-Gomez JD]] | ||
[[Category: Heginbotham | [[Category: Heginbotham L]] | ||
[[Category: Jogini | [[Category: Jogini V]] | ||
[[Category: Kutluay | [[Category: Kutluay E]] | ||
[[Category: Roux | [[Category: Roux B]] | ||
[[Category: Zhao | [[Category: Zhao Y]] | ||
Latest revision as of 12:58, 30 August 2023
Potassium channel kcsa-fab complex with tetrabutylammonium (TBA)Potassium channel kcsa-fab complex with tetrabutylammonium (TBA)
Structural highlights
FunctionKCSA_STRLI Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+).[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe mechanism of intracellular blockade of the KcsA potassium channel by tetrabutylammonium (TBA) is investigated through functional, structural and computational studies. Using planar-membrane electrophysiological recordings, we characterize the binding kinetics as well as the dependence on the transmembrane voltage and the concentration of the blocker. It is found that the apparent affinity of the complex is significantly greater than that of any of the eukaryotic K(+) channels studied previously, and that the off-rate increases with the applied transmembrane voltage. In addition, we report a crystal structure of the KcsA-TBA complex at 2.9 A resolution, with TBA bound inside the large hydrophobic cavity located at the center of the channel, consistent with the results of previous functional and structural studies. Of particular interest is the observation that the presence of TBA has a negligible effect on the channel structure and on the position of the potassium ions occupying the selectivity filter. Inspection of the electron density corresponding to TBA suggests that the ligand may adopt more than one conformation in the complex, though the moderate resolution of the data precludes a definitive interpretation on the basis of the crystallographic refinement methods alone. To provide a rationale for these observations, we carry out an extensive conformational sampling of an atomic model of TBA bound in the central cavity of KcsA, using the Hamiltonian replica-exchange molecular dynamics simulation method. Comparison of the simulated and experimental density maps indicates that the latter does reflect at least two distinct binding orientations of TBA. The simulations show also that the relative population of these binding modes is dependent on the ion configuration occupying the selectivity filter, thus providing a clue to the nature of the voltage-dependence of the binding kinetics. Mechanism of intracellular block of the KcsA K+ channel by tetrabutylammonium: insights from X-ray crystallography, electrophysiology and replica-exchange molecular dynamics simulations.,Faraldo-Gomez JD, Kutluay E, Jogini V, Zhao Y, Heginbotham L, Roux B J Mol Biol. 2007 Jan 19;365(3):649-62. Epub 2006 Sep 29. PMID:17070844[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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