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- | {{Seed}} | |
- | [[Image:3l9w.jpg|left|200px]] | |
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- | <!-- | + | ==KefC C-terminal domain in complex with KefF and GSH== |
- | The line below this paragraph, containing "STRUCTURE_3l9w", creates the "Structure Box" on the page.
| + | <StructureSection load='3l9w' size='340' side='right'caption='[[3l9w]], [[Resolution|resolution]] 1.75Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3l9w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L9W FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | {{STRUCTURE_3l9w| PDB=3l9w | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l9w OCA], [https://pdbe.org/3l9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l9w RCSB], [https://www.ebi.ac.uk/pdbsum/3l9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l9w ProSAT]</span></td></tr> |
| + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/KEFC_ECOLI KEFC_ECOLI] Transport system that facilitates potassium-efflux, possibly by potassium-proton antiport.[https://www.uniprot.org/uniprot/KEFF_ECOLI KEFF_ECOLI] Regulatory subunit of a potassium efflux system that confers protection against electrophiles. Required for full activity of KefC. Shows redox enzymatic activity, but this enzymatic activity is not required for activation of KefC. Can use a wide range of substrates, including electrophilic quinones, and its function could be to reduce the redox toxicity of electrophilic quinones in parallel with acting as triggers for the KefC efflux system.[HAMAP-Rule:MF_01414]<ref>PMID:11053405</ref> <ref>PMID:19523906</ref> <ref>PMID:21742892</ref> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | Gram negative pathogens are protected against toxic electrophilic compounds by glutathione-gated potassium efflux systems (Kef) that modulate cytoplasmic pH. We have elucidated the mechanism of gating through structural and functional analysis of Escherichia coli KefC. The revealed mechanism can explain how subtle chemical differences in glutathione derivatives can produce opposite effects on channel function. Kef channels are regulated by potassium transport and NAD-binding (KTN) domains that sense both reduced glutathione, which inhibits Kef activity, and glutathione adducts that form during electrophile detoxification and activate Kef. We find that reduced glutathione stabilizes an interdomain association between two KTN folds, whereas large adducts sterically disrupt this interaction. F441 is identified as the pivotal residue discriminating between reduced glutathione and its conjugates. We demonstrate a major structural change on the binding of an activating ligand to a KTN-domain protein. Analysis of the regulatory interactions suggests strategies to disrupt pathogen potassium and pH homeostasis. |
| | | |
- | ===KefC C-terminal domain in complex with KefF and GSH===
| + | Mechanism of ligand-gated potassium efflux in bacterial pathogens.,Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR Proc Natl Acad Sci U S A. 2010 Nov 1. PMID:21041667<ref>PMID:21041667</ref> |
| | | |
- | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
- | <!--
| + | </div> |
- | The line below this paragraph, {{ABSTRACT_PUBMED_21041667}}, adds the Publication Abstract to the page
| + | <div class="pdbe-citations 3l9w" style="background-color:#fffaf0;"></div> |
- | (as it appears on PubMed at http://www.pubmed.gov), where 21041667 is the PubMed ID number.
| + | == References == |
- | -->
| + | <references/> |
- | {{ABSTRACT_PUBMED_21041667}}
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | [[Category: Escherichia coli K-12]] |
- | 3L9W is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L9W OCA].
| + | [[Category: Large Structures]] |
- | | + | [[Category: Roosild TP]] |
- | ==Reference== | + | |
- | <ref group="xtra">PMID:21041667</ref><references group="xtra"/> | + | |
- | [[Category: Escherichia coli]] | + | |
- | [[Category: Roosild, T P.]] | + | |
- | [[Category: Antiport]] | + | |
- | [[Category: Cell inner membrane]]
| + | |
- | [[Category: Cell membrane]]
| + | |
- | [[Category: Glutathione]]
| + | |
- | [[Category: Ion transport]]
| + | |
- | [[Category: Membrane]]
| + | |
- | [[Category: Potassium]]
| + | |
- | [[Category: Potassium channel regulation]]
| + | |
- | [[Category: Potassium efflux]]
| + | |
- | [[Category: Potassium transport]]
| + | |
- | [[Category: Transmembrane]]
| + | |
- | [[Category: Transport]]
| + | |
- | [[Category: Transport protein]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Nov 18 00:49:26 2010''
| + | |
| Structural highlights
3l9w is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Method: | X-ray diffraction, Resolution 1.75Å |
Ligands: | , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
KEFC_ECOLI Transport system that facilitates potassium-efflux, possibly by potassium-proton antiport.KEFF_ECOLI Regulatory subunit of a potassium efflux system that confers protection against electrophiles. Required for full activity of KefC. Shows redox enzymatic activity, but this enzymatic activity is not required for activation of KefC. Can use a wide range of substrates, including electrophilic quinones, and its function could be to reduce the redox toxicity of electrophilic quinones in parallel with acting as triggers for the KefC efflux system.[HAMAP-Rule:MF_01414][1] [2] [3]
Publication Abstract from PubMed
Gram negative pathogens are protected against toxic electrophilic compounds by glutathione-gated potassium efflux systems (Kef) that modulate cytoplasmic pH. We have elucidated the mechanism of gating through structural and functional analysis of Escherichia coli KefC. The revealed mechanism can explain how subtle chemical differences in glutathione derivatives can produce opposite effects on channel function. Kef channels are regulated by potassium transport and NAD-binding (KTN) domains that sense both reduced glutathione, which inhibits Kef activity, and glutathione adducts that form during electrophile detoxification and activate Kef. We find that reduced glutathione stabilizes an interdomain association between two KTN folds, whereas large adducts sterically disrupt this interaction. F441 is identified as the pivotal residue discriminating between reduced glutathione and its conjugates. We demonstrate a major structural change on the binding of an activating ligand to a KTN-domain protein. Analysis of the regulatory interactions suggests strategies to disrupt pathogen potassium and pH homeostasis.
Mechanism of ligand-gated potassium efflux in bacterial pathogens.,Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR Proc Natl Acad Sci U S A. 2010 Nov 1. PMID:21041667[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miller S, Ness LS, Wood CM, Fox BC, Booth IR. Identification of an ancillary protein, YabF, required for activity of the KefC glutathione-gated potassium efflux system in Escherichia coli. J Bacteriol. 2000 Nov;182(22):6536-40. PMID:11053405 doi:10.1128/JB.182.22.6536-6540.2000
- ↑ Roosild TP, Castronovo S, Miller S, Li C, Rasmussen T, Bartlett W, Gunasekera B, Choe S, Booth IR. KTN (RCK) domains regulate K+ channels and transporters by controlling the dimer-hinge conformation. Structure. 2009 Jun 10;17(6):893-903. PMID:19523906 doi:10.1016/j.str.2009.03.018
- ↑ Lyngberg L, Healy J, Bartlett W, Miller S, Conway SJ, Booth IR, Rasmussen T. KefF, the regulatory subunit of the potassium efflux system KefC, shows quinone oxidoreductase activity. J Bacteriol. 2011 Sep;193(18):4925-32. PMID:21742892 doi:10.1128/JB.05272-11
- ↑ Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR. Mechanism of ligand-gated potassium efflux in bacterial pathogens. Proc Natl Acad Sci U S A. 2010 Nov 1. PMID:21041667 doi:10.1073/pnas.1012716107
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