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4wbo
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4wbo is ON HOLD Authors: Homan, K.T., Tesmer, J.J.G. Description: Bovine G Protein Coupled Receptor Kinase 1 in Complex with Amlexanox) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Bovine G Protein Coupled Receptor Kinase 1 in Complex with Amlexanox== | |
| + | <StructureSection load='4wbo' size='340' side='right'caption='[[4wbo]], [[Resolution|resolution]] 2.81Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4wbo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WBO 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]] 2.81Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANW:2-AMINO-7-(1-METHYLETHYL)-5-OXO-5H-CHROMENO[2,3-B]PYRIDINE-3-CARBOXYLIC+ACID'>ANW</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=4wbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wbo OCA], [https://pdbe.org/4wbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wbo RCSB], [https://www.ebi.ac.uk/pdbsum/4wbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wbo ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GRK1_BOVIN GRK1_BOVIN] Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade (PubMed:12686556, PubMed:16675451, PubMed:21299498). This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination (By similarity). May play a role in the maintenance of the outer nuclear layer in the retina (By similarity).[UniProtKB:Q9WVL4]<ref>PMID:12686556</ref> <ref>PMID:16675451</ref> <ref>PMID:21299498</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | G protein-coupled receptor kinases (GRKs) have been implicated in human diseases ranging from heart failure to diabetes. Previous studies have identified several compounds that selectively inhibit GRK2, such as paroxetine and balanol. Far fewer selective inhibitors have been reported for GRK5, a target for the treatment of cardiac hypertrophy, and the mechanism of action of reported compounds is unknown. To identify novel scaffolds that selectively inhibit GRK5, a differential scanning fluorometry screen was used to probe a library of 4480 compounds. The best hit was amlexanox, an FDA-approved anti-inflammatory, anti-allergic immunomodulator. The crystal structure of amlexanox in complex with GRK1 demonstrates that its tricyclic aromatic ring system forms ATP-like interactions with the hinge of the kinase domain, which is likely similar to how this drug binds to IkappaB kinase epsilon (IKKepsilon), another kinase known to be inhibited by this compound. Amlexanox was also able to inhibit myocyte enhancer factor 2 transcriptional activity in neonatal rat ventricular myocytes in a manner consistent with GRK5 inhibition. The GRK1 amlexanox structure thus serves as a springboard for the rational design of inhibitors with improved potency and selectivity for GRK5 and IKKepsilon. | ||
| - | + | Identification and characterization of amlexanox as a g protein-coupled receptor kinase 5 inhibitor.,Homan KT, Wu E, Cannavo A, Koch WJ, Tesmer JJ Molecules. 2014 Oct 22;19(10):16937-49. doi: 10.3390/molecules191016937. PMID:25340299<ref>PMID:25340299</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4wbo" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Rhodopsin kinase|Rhodopsin kinase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bos taurus]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Homan KT]] | ||
| + | [[Category: Tesmer JJG]] | ||
Current revision
Bovine G Protein Coupled Receptor Kinase 1 in Complex with Amlexanox
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