5ci7
From Proteopedia
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| - | ''' | + | ==Structure of ULK1 bound to a selective inhibitor== |
| + | <StructureSection load='5ci7' size='340' side='right' caption='[[5ci7]], [[Resolution|resolution]] 1.74Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ci7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CI7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CI7 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=51W:N-[3-({4-[(3-AMINOPROPYL)AMINO]-5-IODOPYRIMIDIN-2-YL}AMINO)PHENYL]PYRROLIDINE-1-CARBOXAMIDE'>51W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wno|4wno]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=5ci7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ci7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5ci7 RCSB], [http://www.ebi.ac.uk/pdbsum/5ci7 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ULK1_HUMAN ULK1_HUMAN]] Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation.<ref>PMID:18936157</ref> <ref>PMID:21460634</ref> <ref>PMID:21795849</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Energy homeostasis in eukaryotic cells is a complex and fundamental process that is misregulated in several human diseases. A key component of energy regulation is a process called autophagy that involves the recycling of cellular components. There has been much recent interest in studying the mechanism of autophagy to understand an important cellular process and to evaluate the therapeutic potential in targeting autophagy. Activation of a kinase called ULK1 initiates autophagy by driving downstream pathways that lead to the formation of double membrane bound vesicles that surround the cellular contents that are to be degraded. Here, we report the discovery of an inhibitor of ULK1 with improved selectivity and a high-resolution crystal structure of the compound bound to the kinase, which will be useful tools for studying autophagy in cells. | ||
| - | + | Discovery and structure of a new inhibitor scaffold of the autophagy initiating kinase ULK1.,Lazarus MB, Shokat KM Bioorg Med Chem. 2015 Jul 26. pii: S0968-0896(15)00618-5. doi:, 10.1016/j.bmc.2015.07.034. PMID:26275681<ref>PMID:26275681</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| - | [[Category: Lazarus, M | + | __TOC__ |
| - | [[Category: Shokat, K | + | </StructureSection> |
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
| + | [[Category: Lazarus, M B]] | ||
| + | [[Category: Shokat, K M]] | ||
| + | [[Category: Autophagy]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 13:26, 26 August 2015
Structure of ULK1 bound to a selective inhibitor
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