6yaa - Revision history

OCA at 13:22, 24 January 2024

OCA — Wed, 24 Jan 2024 13:22:55 GMT

←Older revision		Revision as of 13:22, 24 January 2024
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	==Structure of the (SR) Ca2+-ATPase bound to the inhibitor compound CAD204520 and TNP-ATP==		==Structure of the (SR) Ca2+-ATPase bound to the inhibitor compound CAD204520 and TNP-ATP==
-	<StructureSection load='6yaa' size='340' side='right'caption='[[6yaa]]' scene=''>	+	<StructureSection load='6yaa' size='340' side='right'caption='[[6yaa]], [[Resolution\|resolution]] 3.40Å' 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=6YAA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6YAA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yaa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YAA 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=6yaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yaa OCA], [~~http~~://pdbe.org/6yaa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6yaa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6yaa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6yaa ProSAT]</span></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]] 3.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=128:SPIRO(2,4,6-TRINITROBENZENE[1,2A]-2O,3O-METHYLENE-ADENINE-TRIPHOSPHATE'>128</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=OHW:4-[2-[(2~{R})-2-[3-propyl-6-(trifluoromethyloxy)-1~{H}-indol-2-yl]piperidin-1-yl]ethyl]morpholine'>OHW</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=6yaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yaa OCA], [https://pdbe.org/6yaa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yaa RCSB], [https://www.ebi.ac.uk/pdbsum/6yaa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yaa ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/AT2A1_RABIT AT2A1_RABIT] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The identification of SERCA (sarco/endoplasmic reticulum calcium ATPase) as a target for modulating gain-of-function NOTCH1 mutations in Notch-dependent cancers has spurred the development of this compound class for cancer therapeutics. Despite the innate toxicity challenge associated with SERCA inhibition, we identified CAD204520, a small molecule with better drug-like properties and reduced off-target Ca(2+) toxicity compared with the SERCA inhibitor thapsigargin. In this work, we describe the properties and complex structure of CAD204520 and show that CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T cell acute lymphoblastic leukemia (T-ALL) and mantle cell lymphoma (MCL). Uniquely among SERCA inhibitors, CAD204520 suppresses NOTCH1-mutated leukemic cells in a T-ALL xenografted model without causing cardiac toxicity. This study supports the development of SERCA inhibitors for Notch-dependent cancers and extends their application to cases with isolated mutations in the PEST degradation domain of NOTCH1, such as MCL or chronic lymphocytic leukemia (CLL).
		+
		+	Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia.,Marchesini M, Gherli A, Montanaro A, Patrizi L, Sorrentino C, Pagliaro L, Rompietti C, Kitara S, Heit S, Olesen CE, Moller JV, Savi M, Bocchi L, Vilella R, Rizzi F, Baglione M, Rastelli G, Loiacono C, La Starza R, Mecucci C, Stegmaier K, Aversa F, Stilli D, Lund Winther AM, Sportoletti P, Bublitz M, Dalby-Brown W, Roti G Cell Chem Biol. 2020 Apr 15. pii: S2451-9456(20)30116-1. doi:, 10.1016/j.chembiol.2020.04.002. PMID:32386594<ref>PMID:32386594</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6yaa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[ATPase 3D structures\|ATPase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Oryctolagus cuniculus]]
	[[Category: Aversa F]]		[[Category: Aversa F]]
	[[Category: Baglione M]]		[[Category: Baglione M]]

OCA at 05:52, 20 May 2020

OCA — Wed, 20 May 2020 05:52:44 GMT

←Older revision		Revision as of 05:52, 20 May 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6yaa is ~~ON HOLD until Paper Publication~~	+	==Structure of the (SR) Ca2+-ATPase bound to the inhibitor compound CAD204520 and TNP-ATP==
-		+	<StructureSection load='6yaa' size='340' side='right'caption='[[6yaa]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YAA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YAA FirstGlance]. <br>
-	~~Description~~:	+	</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=6yaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yaa OCA], [http://pdbe.org/6yaa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yaa RCSB], [http://www.ebi.ac.uk/pdbsum/6yaa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yaa ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Aversa F]]
		+	[[Category: Baglione M]]
		+	[[Category: Bocchi L]]
		+	[[Category: Bublitz M]]
		+	[[Category: Dalby-Brown W]]
		+	[[Category: Gherli A]]
		+	[[Category: Heit S]]
		+	[[Category: Kitara S]]
		+	[[Category: La Starza R]]
		+	[[Category: Loiacona C]]
		+	[[Category: Lund Winther AM]]
		+	[[Category: Marchesini M]]
		+	[[Category: Mecucci C]]
		+	[[Category: Moller JV]]
		+	[[Category: Montanaro A]]
		+	[[Category: Olesen CE]]
		+	[[Category: Pagliaro L]]
		+	[[Category: Patrizi L]]
		+	[[Category: Rastelli G]]
		+	[[Category: Rizzi F]]
		+	[[Category: Rompietti C]]
		+	[[Category: Roti G]]
		+	[[Category: Savi M]]
		+	[[Category: Sorrentino C]]
		+	[[Category: Sportoletti P]]
		+	[[Category: Stegmair K]]
		+	[[Category: Stilli D]]
		+	[[Category: Vilella R]]

OCA at 08:32, 27 March 2020

OCA — Fri, 27 Mar 2020 08:32:37 GMT

←Older revision		Revision as of 08:32, 27 March 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6yaa is ON HOLD	+	The entry 6yaa is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 18 Mar 2020 08:40:56 GMT

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

←Older revision

Revision as of 08:40, 18 March 2020

OCA: New page: '''Unreleased structure''' The entry 6yaa is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Mar 2020 08:40:55 GMT

New page: '''Unreleased structure''' The entry 6yaa is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6yaa is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]