6eeb
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Calmodulin in complex with malbrancheamide== |
| + | <StructureSection load='6eeb' size='340' side='right'caption='[[6eeb]], [[Resolution|resolution]] 1.96Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6eeb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EEB FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=J6P:(5aS,12aS,13aS)-8,9-dichloro-12,12-dimethyl-2,3,11,12,12a,13-hexahydro-1H,5H,6H-5a,13a-(epiminomethano)indolizino[7,6-b]carbazol-14-one'>J6P</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6eeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eeb OCA], [http://pdbe.org/6eeb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eeb RCSB], [http://www.ebi.ac.uk/pdbsum/6eeb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eeb 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/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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | G protein-coupled receptor (GPCR) kinases (GRKs) are responsible for initiating desensitization of activated GPCRs. GRK5 is potently inhibited by the calcium-sensing protein calmodulin (CaM), which leads to nuclear translocation of GRK5 and promotion of cardiac hypertrophy. Herein, we report the architecture of the Ca(2+).CaM-GRK5 complex determined by small-angle X-ray scattering and negative-stain electron microscopy. Ca(2+).CaM binds primarily to the small lobe of the kinase domain of GRK5 near elements critical for receptor interaction and membrane association, thereby inhibiting receptor phosphorylation while activating the kinase for phosphorylation of soluble substrates. To define the role of each lobe of Ca(2+).CaM, we utilized the natural product malbrancheamide as a chemical probe to show that the C-terminal lobe of Ca(2+).CaM regulates membrane binding while the N-terminal lobe regulates receptor phosphorylation and kinase domain activation. In cells, malbrancheamide attenuated GRK5 nuclear translocation and effectively blocked the hypertrophic response, demonstrating the utility of this natural product and its derivatives in probing Ca(2+).CaM-dependent hypertrophy. | ||
| - | + | Perturbation of the interactions of calmodulin with GRK5 using a natural product chemical probe.,Beyett TS, Fraley AE, Labudde E, Patra D, Coleman RC, Eguchi A, Glukhova A, Chen Q, Williams RM, Koch WJ, Sherman DH, Tesmer JJG Proc Natl Acad Sci U S A. 2019 Jul 23. pii: 1818547116. doi:, 10.1073/pnas.1818547116. PMID:31337679<ref>PMID:31337679</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6eeb" style="background-color:#fffaf0;"></div> |
| - | [[Category: Fraley, A | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Beyett, T S]] | ||
| + | [[Category: Fraley, A E]] | ||
| + | [[Category: Tesmer, J J.G]] | ||
| + | [[Category: Ef hand]] | ||
| + | [[Category: Metal binding protein]] | ||
Revision as of 05:47, 7 August 2019
Calmodulin in complex with malbrancheamide
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