7umo
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of Unc119-inhibitor complex.== | |
| + | <StructureSection load='7umo' size='340' side='right'caption='[[7umo]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7umo]] is a 6 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=7UMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UMO 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]] 2.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NT6:(3s,5s,7s)-N-(4,5-dichloropyridin-2-yl)adamantane-1-carboxamide'>NT6</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=7umo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7umo OCA], [https://pdbe.org/7umo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7umo RCSB], [https://www.ebi.ac.uk/pdbsum/7umo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7umo ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN] Idiopathic CD4 lymphocytopenia;Cone rod dystrophy. Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light-sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN] Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Binds myristoylated NPHP3; however, in contrast to UNC119B, does not seem to play a major role in ciliary membrane localization of NPHP3. Does not bind all myristoylated proteins. Probably plays a role in trafficking proteins in photoreceptor cells.<ref>PMID:22085962</ref> <ref>PMID:21642972</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Insulin resistance (IR) is the root cause of type II diabetes, yet no safe treatment is available to address it. Using a high throughput compatible assay that measures real-time translocation of the glucose transporter glucose transporter 4 (GLUT4), we identified small molecules that potentiate insulin action. In vivo, these insulin sensitizers improve insulin-stimulated GLUT4 translocation, glucose tolerance, and glucose uptake in a model of IR. Using proteomic and CRISPR-based approaches, we identified the targets of those compounds as Unc119 proteins and solved the structure of Unc119 bound to the insulin sensitizer. This study identifies compounds that have the potential to be developed into diabetes treatment and establishes Unc119 proteins as targets for improving insulin sensitivity. | ||
| - | + | Insulin sensitization by small molecules enhancing GLUT4 translocation.,Yin TC, Van Vranken JG, Srivastava D, Mittal A, Buscaglia P, Moore AE, Verdinez JA, Graham AE, Walsh SA, Acevedo MA, Kerns RJ, Artemyev NO, Gygi SP, Sebag JA Cell Chem Biol. 2023 Jun 28:S2451-9456(23)00190-3. doi: , 10.1016/j.chembiol.2023.06.012. PMID:37453421<ref>PMID:37453421</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7umo" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Artemyev NO]] | ||
| + | [[Category: Sebag JA]] | ||
| + | [[Category: Srivastava D]] | ||
Current revision
Structure of Unc119-inhibitor complex.
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