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4wnp

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Revision as of 10:50, 11 August 2016

Structure of ULK1 bound to a potent inhibitor

Structural highlights

4wnp is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	4wno
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Autophagy is a conserved cellular process that involves the degradation of cellular components for energy maintenance and cytoplasmic quality control that has recently gained interest as a novel target for a variety of human diseases, including cancer. A prime candidate to determine the potential therapeutic benefit of targeting autophagy is the kinase ULK1, whose activation initiates autophagy. Here, we report the first structures of ULK1, in complex with multiple potent inhibitors. These structures show features unique to the enzyme and will provide a path for the rational design of selective compounds as cellular probes and potential therapeutics.

Structure of the Human Autophagy Initiating Kinase ULK1 in Complex with Potent Inhibitors.,Lazarus MB, Novotny CJ, Shokat KM ACS Chem Biol. 2015 Jan 6. PMID:25551253^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol. 2009 Jan;29(1):157-71. doi: 10.1128/MCB.01082-08. Epub 2008 Oct, 20. PMID:18936157 doi:http://dx.doi.org/10.1128/MCB.01082-08
↑ Loffler AS, Alers S, Dieterle AM, Keppeler H, Franz-Wachtel M, Kundu M, Campbell DG, Wesselborg S, Alessi DR, Stork B. Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy. 2011 Jul;7(7):696-706. Epub 2011 Jul 1. PMID:21460634
↑ Jung CH, Seo M, Otto NM, Kim DH. ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy. 2011 Oct;7(10):1212-21. doi: 10.4161/auto.7.10.16660. Epub 2011 Oct 1. PMID:21795849 doi:http://dx.doi.org/10.4161/auto.7.10.16660
↑ Lazarus MB, Novotny CJ, Shokat KM. Structure of the Human Autophagy Initiating Kinase ULK1 in Complex with Potent Inhibitors. ACS Chem Biol. 2015 Jan 6. PMID:25551253 doi:http://dx.doi.org/10.1021/cb500835z

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4wnp"

@@ Line 1: / Line 1: @@
 ==Structure of ULK1 bound to a potent inhibitor==
 <StructureSection load='4wnp' size='340' side='right' caption='[[4wnp]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <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=4wnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wnp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wnp RCSB], [http://www.ebi.ac.uk/pdbsum/4wnp PDBsum]</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=4wnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wnp OCA], [http://pdbe.org/4wnp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wnp RCSB], [http://www.ebi.ac.uk/pdbsum/4wnp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wnp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4wnp" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
 == References ==
 <references/>

4wnp

From Proteopedia

Revision as of 10:50, 11 August 2016

Structure of ULK1 bound to a potent inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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