5ci7

From Proteopedia

(Difference between revisions)

Revision as of 16:00, 11 December 2019

Structure of ULK1 bound to a selective inhibitor

Structural highlights

5ci7 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	4wno
Gene:	ULK1, KIAA0722 (HUMAN)
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

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^[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, Shokat KM. Discovery and structure of a new inhibitor scaffold of the autophagy initiating kinase ULK1. Bioorg Med Chem. 2015 Jul 26. pii: S0968-0896(15)00618-5. doi:, 10.1016/j.bmc.2015.07.034. PMID:26275681 doi:http://dx.doi.org/10.1016/j.bmc.2015.07.034

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/5ci7"

@@ Line 1: / Line 1: @@
 ==Structure of ULK1 bound to a selective inhibitor==
-<StructureSection load='5ci7' size='340' side='right' caption='[[5ci7]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
+<StructureSection load='5ci7' size='340' side='right'caption='[[5ci7]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5ci7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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>
@@ Line 22: / Line 22: @@
 </div>
 <div class="pdbe-citations 5ci7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 == References ==
 <references/>
@@ Line 27: / Line 30: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Lazarus, M B]]

5ci7

From Proteopedia

Revision as of 16:00, 11 December 2019

Structure of ULK1 bound to a selective inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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