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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7xnn]] is a 8 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=7XNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XNN FirstGlance]. <br>
<table><tr><td colspan='2'>[[7xnn]] is a 8 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=7XNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XNN FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I0S:(2R)-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-1-(4-methylbenzene-1-sulfonyl)piperidine-2-carboxamide'>I0S</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I0S:(2R)-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-1-(4-methylbenzene-1-sulfonyl)piperidine-2-carboxamide'>I0S</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</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=7xnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xnn OCA], [https://pdbe.org/7xnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xnn RCSB], [https://www.ebi.ac.uk/pdbsum/7xnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xnn 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=7xnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xnn OCA], [https://pdbe.org/7xnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xnn RCSB], [https://www.ebi.ac.uk/pdbsum/7xnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xnn ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[https://www.uniprot.org/uniprot/CALM3_HUMAN CALM3_HUMAN] Catecholaminergic polymorphic ventricular tachycardia;Romano-Ward syndrome. The disease may be caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
[https://www.uniprot.org/uniprot/CALM3_HUMAN CALM3_HUMAN] Romano-Ward syndrome;Catecholaminergic polymorphic ventricular tachycardia. The disease may be caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/CALM3_HUMAN CALM3_HUMAN] Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:31454269). Calcium-binding is required for the activation of calmodulin (PubMed:35568036, PubMed:16760425, PubMed:31454269). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425).<ref>PMID:16760425</ref> <ref>PMID:31454269</ref> <ref>PMID:35568036</ref>  (Microbial infection) Required for C.violaceum CopC arginine ADP-riboxanase activity.<ref>PMID:35338844</ref> <ref>PMID:35446120</ref>  
[https://www.uniprot.org/uniprot/CALM3_HUMAN CALM3_HUMAN] Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:31454269). Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:31454269, PubMed:35568036). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425).<ref>PMID:16760425</ref> <ref>PMID:31454269</ref> <ref>PMID:35568036</ref>  (Microbial infection) Required for C.violaceum CopC and S.flexneri OspC3 arginine ADP-riboxanase activity.<ref>PMID:35338844</ref> <ref>PMID:35446120</ref> <ref>PMID:36423631</ref> <ref>PMID:36624349</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cardiac KCNQ1 potassium channel carries the important I(Ks) current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 structures have been recently resolved, the structural basis for the dynamic electro-mechanical coupling, also known as the voltage sensor domain-pore domain (VSD-PD) coupling, remains largely unknown. In this study, utilizing two VSD-PD coupling enhancers, namely, the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) and a small-molecule ML277, we determined 2.5-3.5 A resolution cryo-electron microscopy structures of full-length human KCNQ1-calmodulin (CaM) complex in the apo closed, ML277-bound open, and ML277-PIP(2)-bound open states. ML277 binds at the "elbow" pocket above the S4-S5 linker and directly induces an upward movement of the S4-S5 linker and the opening of the activation gate without affecting the C-terminal domain (CTD) of KCNQ1. PIP(2) binds at the cleft between the VSD and the PD and brings a large structural rearrangement of the CTD together with the CaM to activate the PD. These findings not only elucidate the structural basis for the dynamic VSD-PD coupling process during KCNQ1 gating but also pave the way to develop new therapeutics for anti-arrhythmia.
 
Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers.,Ma D, Zhong L, Yan Z, Yao J, Zhang Y, Ye F, Huang Y, Lai D, Yang W, Hou P, Guo J Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2207067119. doi: , 10.1073/pnas.2207067119. Epub 2022 Nov 3. PMID:36763058<ref>PMID:36763058</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xnn" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
== References ==
== References ==
<references/>
<references/>

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