6yid - Revision history

OCA at 13:27, 24 January 2024

2024-01-24T13:27:37Z

←Older revision		Revision as of 13:27, 24 January 2024
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	<StructureSection load='6yid' size='340' side='right'caption='[[6yid]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='6yid' size='340' side='right'caption='[[6yid]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6yid]] is a 4 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=6YID OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6YID FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yid]] is a 4 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=6YID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YID FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=EDJ:2-({5-bromo-2~~-[~~(3,4,5-trimethoxyphenyl)amino~~]~~pyrimidin-4-yl}oxy)-N-methylbenzene-1-carboximidic+acid'>EDJ</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.7Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>ULK2, KIAA0623 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDJ:2-({5-bromo-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}oxy)-N-methylbenzene-1-carboximidic+acid'>EDJ</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6yid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yid OCA], [https://pdbe.org/6yid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yid RCSB], [https://www.ebi.ac.uk/pdbsum/6yid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yid ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6yid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yid OCA], [~~http~~://pdbe.org/6yid PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6yid RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6yid PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6yid ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ULK2_HUMAN ULK2_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 a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.<ref>PMID:18936157</ref> <ref>PMID:21460634</ref> <ref>PMID:21460635</ref> <ref>PMID:21690395</ref> <ref>PMID:21795849</ref>	+	[https://www.uniprot.org/uniprot/ULK2_HUMAN ULK2_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 a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.<ref>PMID:18936157</ref> <ref>PMID:21460634</ref> <ref>PMID:21460635</ref> <ref>PMID:21690395</ref> <ref>PMID:21795849</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Bakas NA]]
-	[[Category: Bakas~~, N A~~]]	+	[[Category: Chaikuad A]]
-	[[Category: Chaikuad, A]]	+	[[Category: Cosford NDP]]
-	[[Category: Cosford~~, N D.P~~]]	+	[[Category: Knapp S]]
-	[[Category: Knapp, S]]	+	[[Category: Lambert LJ]]
-	[[Category: Lambert~~, L J~~]]	+	[[Category: Ren H]]
-	[[Category: Ren, H]]	+
-	~~[[Category: Structural genomic]]~~	+
-	~~[[Category: Autophagy]]~~	+
-	~~[[Category: Chemical probe]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Ulk2~~]]	+

OCA at 06:02, 20 January 2021

2021-01-20T06:02:32Z

←Older revision		Revision as of 06:02, 20 January 2021
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	==Crystal structure of ULK2 in complex with SBI-0206965==		==Crystal structure of ULK2 in complex with SBI-0206965==
-	<StructureSection load='6yid' size='340' side='right'caption='[[6yid]]' scene=''>	+	<StructureSection load='6yid' size='340' side='right'caption='[[6yid]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YID OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YID FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yid]] is a 4 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=6YID OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YID FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yid OCA], [http://pdbe.org/6yid PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yid RCSB], [http://www.ebi.ac.uk/pdbsum/6yid PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yid ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDJ:2-({5-bromo-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}oxy)-N-methylbenzene-1-carboximidic+acid'>EDJ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ULK2, KIAA0623 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://proteopedia.org/fgij/fg.htm?mol=6yid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yid OCA], [http://pdbe.org/6yid PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yid RCSB], [http://www.ebi.ac.uk/pdbsum/6yid PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yid ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ULK2_HUMAN ULK2_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 a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.<ref>PMID:18936157</ref> <ref>PMID:21460634</ref> <ref>PMID:21460635</ref> <ref>PMID:21690395</ref> <ref>PMID:21795849</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of autophagy, the major cellular recycling pathway in mammalian cells, is a promising strategy for the treatment of triple-negative breast cancer (TNBC). We previously reported SBI-0206965, a small molecule inhibitor of unc-51-like autophagy activating kinase 1 (ULK1), which is a key regulator of autophagy initiation. Herein, we describe the design, synthesis, and characterization of new dual inhibitors of ULK1 and ULK2 (ULK1/2). One inhibitor, SBP-7455 (compound 26), displayed improved binding affinity for ULK1/2 compared with SBI-0206965, potently inhibited ULK1/2 enzymatic activity in vitro and in cells, reduced the viability of TNBC cells and had oral bioavailability in mice. SBP-7455 inhibited starvation-induced autophagic flux in TNBC cells that were dependent on autophagy for survival and displayed synergistic cytotoxicity with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib against TNBC cells. These data suggest that combining ULK1/2 and PARP inhibition may have clinical utility for the treatment of TNBC.
		+
		+	Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer.,Ren H, Bakas NA, Vamos M, Chaikuad A, Limpert AS, Wimer CD, Brun SN, Lambert LJ, Tautz L, Celeridad M, Sheffler DJ, Knapp S, Shaw RJ, Cosford NDP J Med Chem. 2020 Dec 10;63(23):14609-14625. doi: 10.1021/acs.jmedchem.0c00873., Epub 2020 Nov 17. PMID:33200929<ref>PMID:33200929</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6yid" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bakas NA]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Chaikuad A]]	+	[[Category: Bakas, N A]]
-	[[Category: Cosford ~~NDP~~]]	+	[[Category: Chaikuad, A]]
-	[[Category: Knapp S]]	+	[[Category: Cosford, N D.P]]
-	[[Category: Lambert LJ]]	+	[[Category: Knapp, S]]
-	[[Category: Ren H]]	+	[[Category: Lambert, L J]]
		+	[[Category: Ren, H]]
		+	[[Category: Structural genomic]]
		+	[[Category: Autophagy]]
		+	[[Category: Chemical probe]]
		+	[[Category: Kinase]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Sgc]]
		+	[[Category: Transferase]]
		+	[[Category: Ulk2]]

OCA at 10:17, 17 June 2020

2020-06-17T10:17:17Z

←Older revision		Revision as of 10:17, 17 June 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6yid ~~is ON HOLD~~	+	==Crystal structure of ULK2 in complex with SBI-0206965==
-		+	<StructureSection load='6yid' size='340' side='right'caption='[[6yid]]' scene=''>
-	~~Authors~~: ~~Chaikuad, A~~.~~, Ren, H~~.~~, Bakas, N~~.A., ~~Lambert, L~~.J., ~~Cosford~~, N.D.P., ~~Knapp, S~~., ~~Structural Genomics Consortium (SGC)~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YID OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YID FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of ULK2 in complex with SBI~~-~~0206965~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yid OCA], [http://pdbe.org/6yid PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yid RCSB], [http://www.ebi.ac.uk/pdbsum/6yid PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yid ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Chaikuad, A~~]]	+	__TOC__
-	[[Category: ~~Knapp, S~~]]	+	</StructureSection>
-	[[Category: ~~Lambert, L.J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Bakas, N.A~~]]	+	[[Category: Bakas NA]]
-	[[Category: ~~Structural Genomics Consortium (Sgc)]]~~	+	[[Category: Chaikuad A]]
-	~~[[Category: Cosford, N.D.P~~]]	+	[[Category: Cosford NDP]]
-	[[Category: Ren, H]]	+	[[Category: Knapp S]]
		+	[[Category: Lambert LJ]]
		+	[[Category: Ren H]]

OCA at 04:22, 22 April 2020

2020-04-22T04:22:16Z

←Older revision		Revision as of 04:22, 22 April 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6yid is ON HOLD ~~until sometime in the future~~	+	The entry 6yid is ON HOLD

	Authors: Chaikuad, A., Ren, H., Bakas, N.A., Lambert, L.J., Cosford, N.D.P., Knapp, S., Structural Genomics Consortium (SGC)		Authors: Chaikuad, A., Ren, H., Bakas, N.A., Lambert, L.J., Cosford, N.D.P., Knapp, S., Structural Genomics Consortium (SGC)
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Chaikuad, A]]		[[Category: Chaikuad, A]]
-	[[Category: Bakas, N.A]]
-	[[Category: Ren, H]]
	[[Category: Knapp, S]]		[[Category: Knapp, S]]
	[[Category: Lambert, L.J]]		[[Category: Lambert, L.J]]
		+	[[Category: Bakas, N.A]]
	[[Category: Structural Genomics Consortium (Sgc)]]		[[Category: Structural Genomics Consortium (Sgc)]]
	[[Category: Cosford, N.D.P]]		[[Category: Cosford, N.D.P]]
		+	[[Category: Ren, H]]

OCA: Protected "6yid" [edit=sysop:move=sysop]

2020-04-08T05:45:31Z

Protected "6yid" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:45, 8 April 2020

OCA: New page: '''Unreleased structure''' The entry 6yid is ON HOLD until sometime in the future Authors: Chaikuad, A., Ren, H., Bakas, N.A., Lambert, L.J., Cosford, N.D.P., Knapp, S., Structural Geno...

2020-04-08T05:45:30Z

New page: '''Unreleased structure''' The entry 6yid is ON HOLD until sometime in the future Authors: Chaikuad, A., Ren, H., Bakas, N.A., Lambert, L.J., Cosford, N.D.P., Knapp, S., Structural Geno...

New page

'''Unreleased structure'''

The entry 6yid is ON HOLD until sometime in the future

Authors: Chaikuad, A., Ren, H., Bakas, N.A., Lambert, L.J., Cosford, N.D.P., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of ULK2 in complex with SBI-0206965
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Bakas, N.A]]
[[Category: Ren, H]]
[[Category: Knapp, S]]
[[Category: Lambert, L.J]]
[[Category: Structural Genomics Consortium (Sgc)]]
[[Category: Cosford, N.D.P]]