5wc5: Difference between revisions

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 ==Structural insights into the potency of SK/IK channel positive modulators==
-<StructureSection load='5wc5' size='340' side='right' caption='[[5wc5]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='5wc5' size='340' side='right'caption='[[5wc5]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5wc5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WC5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WC5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5wc5]] is a 2 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=5WC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WC5 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AJV:7-fluoro-3-(hydroxyamino)-2H-indol-2-one'>AJV</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KCNN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CALM1, CALM, CAM, CAM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AJV:7-fluoro-3-(hydroxyamino)-2H-indol-2-one'>AJV</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5wc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc5 OCA], [http://pdbe.org/5wc5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wc5 RCSB], [http://www.ebi.ac.uk/pdbsum/5wc5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc5 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=5wc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc5 OCA], [https://pdbe.org/5wc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wc5 RCSB], [https://www.ebi.ac.uk/pdbsum/5wc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc5 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4.  The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.
 == Function ==
-[[http://www.uniprot.org/uniprot/KCNN2_HUMAN KCNN2_HUMAN]] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin. [[http://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN]] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).<ref>PMID:16760425</ref> <ref>PMID:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref>
+[https://www.uniprot.org/uniprot/KCNN2_HUMAN KCNN2_HUMAN] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Small-conductance Ca(2+)-activated K(+) (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and SKS-14 (7-fluoro-3-(hydroxyimino)indolin-2-one). A combination of x-ray crystallographic, computational and electrophysiological approaches was utilized to investigate the interactions between the positive modulators and their binding pocket. A strong trend exists between the interaction energy of the compounds within their binding site calculated from the crystal structures, and the potency of these compounds in potentiating the SK2 channel current determined by electrophysiological recordings. Our results further reveal that the difference in potency of the positive modulators in potentiating SK2 channel activity may be attributed primarily to specific electrostatic interactions between the modulators and their binding pocket.
-Structural insights into the potency of SK channel positive modulators.,Nam YW, Orfali R, Liu T, Yu K, Cui M, Wulff H, Zhang M Sci Rep. 2017 Dec 7;7(1):17178. doi: 10.1038/s41598-017-16607-8. PMID:29214998<ref>PMID:29214998</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 5wc5" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Calmodulin|Calmodulin]]
+*[[Calmodulin 3D structures|Calmodulin 3D structures]]
-== References ==
+*[[Potassium channel 3D structures|Potassium channel 3D structures]]
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Nam, Y W]]
+[[Category: Large Structures]]
-[[Category: Zhang, M]]
+[[Category: Nam YW]]
-[[Category: Calcium binding protein]]
+[[Category: Zhang M]]
-[[Category: Metal transport]]