7bht - Revision history

OCA at 07:48, 1 May 2024

2024-05-01T07:48:20Z

←Older revision		Revision as of 07:48, 1 May 2024
Line 3:		Line 3:
	<StructureSection load='7bht' size='340' side='right'caption='[[7bht]], [[Resolution\|resolution]] 1.05Å' scene=''>		<StructureSection load='7bht' size='340' side='right'caption='[[7bht]], [[Resolution\|resolution]] 1.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7bht]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7bht]] is a 1 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=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=TO8:7-chloranyl-4-(dimethylamino)-1~{H}-quinazolin-2-one'>TO8</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]] 1.052Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAT2A, AMS2, MATA2 ([https://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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=TO8:7-chloranyl-4-(dimethylamino)-1~{H}-quinazolin-2-one'>TO8</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht ProSAT]</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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.	+	[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	MAT2a is a methionine adenosyltransferase that synthesizes the essential metabolite S-adenosylmethionine (SAM) from methionine and ATP. Tumors bearing the co-deletion of p16 and MTAP genes have been shown to be sensitive to MAT2a inhibition, making it an attractive target for treatment of MTAP-deleted cancers. A fragment-based lead generation campaign identified weak but efficient hits binding in a known allosteric site. By use of structure-guided design and systematic SAR exploration, the hits were elaborated through a merging and growing strategy into an arylquinazolinone series of potent MAT2a inhibitors. The selected in vivo tool compound 28 reduced SAM-dependent methylation events in cells and inhibited proliferation of MTAP-null cells in vitro. In vivo studies showed that 28 was able to induce antitumor response in an MTAP knockout HCT116 xenograft model.	+

-	Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model.,De Fusco C, Schimpl M, Borjesson U, Cheung T, Collie I, Evans L, Narasimhan P, Stubbs C, Vazquez-Chantada M, Wagner DJ, Grondine M, Sanders MG, Tentarelli S, Underwood E, Argyrou A, Smith JM, Lynch JT, Chiarparin E, Robb G, Bagal SK, Scott JS J Med Chem. 2021 Apr 26. doi: 10.1021/acs.jmedchem.1c00067. PMID:33900758<ref>PMID:33900758</ref>	+	==See Also==
-		+	*[[S-adenosylmethionine synthetase 3D structures\|S-adenosylmethionine synthetase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 7bht" style~~=~~"background-color:#fffaf0;"></div>~~	+
-	~~== References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Methionine adenosyltransferase]]~~	+	[[Category: Argyrou A]]
-	[[Category: Argyrou, A]]	+	[[Category: Bagal S]]
-	[[Category: Bagal, S]]	+	[[Category: Borjesson U]]
-	[[Category: Borjesson, U]]	+	[[Category: Cheung T]]
-	[[Category: Cheung, T]]	+	[[Category: Chiarparin E]]
-	[[Category: Chiarparin, E]]	+	[[Category: Collie I]]
-	[[Category: Collie, I]]	+	[[Category: De Fusco C]]
-	[[Category: ~~Evans, L~~]]	+	[[Category: Evans L]]
-	[[Category: ~~Fusco, C De~~]]	+	[[Category: Grondine M]]
-	[[Category: Grondine, M]]	+	[[Category: Narasimhan P]]
-	[[Category: Narasimhan, P]]	+	[[Category: Robb G]]
-	[[Category: Robb, G]]	+	[[Category: Schimpl M]]
-	[[Category: Schimpl, M]]	+	[[Category: Scott JS]]
-	[[Category: Scott~~, J S~~]]	+	[[Category: Stubbs C]]
-	[[Category: Stubbs, C]]	+	[[Category: Tentarelli S]]
-	[[Category: Tentarelli, S]]	+	[[Category: Underwood E]]
-	[[Category: Underwood, E]]	+	[[Category: Vazquez-Chantada M]]
-	[[Category: Vazquez-Chantada, M]]	+	[[Category: Wagner DJ]]
-	[[Category: Wagner~~, D J]]~~	+
-	~~[[Category: Allosteric inhibitor]]~~	+
-	~~[[Category: Fragment-based drug design]]~~	+
-	~~[[Category: Oncology]]~~	+
-	~~[[Category: Synthetic lethal therapy]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 12:30, 9 June 2021

2021-06-09T12:30:12Z

←Older revision		Revision as of 12:30, 9 June 2021
Line 3:		Line 3:
	<StructureSection load='7bht' size='340' side='right'caption='[[7bht]], [[Resolution\|resolution]] 1.05Å' scene=''>		<StructureSection load='7bht' size='340' side='right'caption='[[7bht]], [[Resolution\|resolution]] 1.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7bht]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7bht]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=TO8:7-chloranyl-4-(dimethylamino)-1~{H}-quinazolin-2-one'>TO8</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=TO8:7-chloranyl-4-(dimethylamino)-1~{H}-quinazolin-2-one'>TO8</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAT2A, AMS2, MATA2 ([https://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'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht ProSAT]</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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Methionine adenosyltransferase]]		[[Category: Methionine adenosyltransferase]]

OCA at 09:07, 5 May 2021

2021-05-05T09:07:43Z

←Older revision		Revision as of 09:07, 5 May 2021
Line 1:		Line 1:

	==Crystal structure of MAT2a with quinazolinone fragment 5 bound in the allosteric site==		==Crystal structure of MAT2a with quinazolinone fragment 5 bound in the allosteric site==
-	<StructureSection load='7bht' size='340' side='right'caption='[[7bht]]' scene=''>	+	<StructureSection load='7bht' size='340' side='right'caption='[[7bht]], [[Resolution\|resolution]] 1.05Å' 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=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7bht]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>
-	</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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=TO8:7-chloranyl-4-(dimethylamino)-1~{H}-quinazolin-2-one'>TO8</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/METK2_HUMAN METK2_HUMAN]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	MAT2a is a methionine adenosyltransferase that synthesizes the essential metabolite S-adenosylmethionine (SAM) from methionine and ATP. Tumors bearing the co-deletion of p16 and MTAP genes have been shown to be sensitive to MAT2a inhibition, making it an attractive target for treatment of MTAP-deleted cancers. A fragment-based lead generation campaign identified weak but efficient hits binding in a known allosteric site. By use of structure-guided design and systematic SAR exploration, the hits were elaborated through a merging and growing strategy into an arylquinazolinone series of potent MAT2a inhibitors. The selected in vivo tool compound 28 reduced SAM-dependent methylation events in cells and inhibited proliferation of MTAP-null cells in vitro. In vivo studies showed that 28 was able to induce antitumor response in an MTAP knockout HCT116 xenograft model.
		+
		+	Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model.,De Fusco C, Schimpl M, Borjesson U, Cheung T, Collie I, Evans L, Narasimhan P, Stubbs C, Vazquez-Chantada M, Wagner DJ, Grondine M, Sanders MG, Tentarelli S, Underwood E, Argyrou A, Smith JM, Lynch JT, Chiarparin E, Robb G, Bagal SK, Scott JS J Med Chem. 2021 Apr 26. doi: 10.1021/acs.jmedchem.1c00067. PMID:33900758<ref>PMID:33900758</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7bht" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Argyrou A]]	+	[[Category: Methionine adenosyltransferase]]
-	[[Category: Bagal S]]	+	[[Category: Argyrou, A]]
-	[[Category: Borjesson U]]	+	[[Category: Bagal, S]]
-	[[Category: Cheung T]]	+	[[Category: Borjesson, U]]
-	[[Category: Chiarparin E]]	+	[[Category: Cheung, T]]
-	[[Category: Collie I]]	+	[[Category: Chiarparin, E]]
-	[[Category: ~~De Fusco C~~]]	+	[[Category: Collie, I]]
-	[[Category: ~~Evans L~~]]	+	[[Category: Evans, L]]
-	[[Category: Grondine M]]	+	[[Category: Fusco, C De]]
-	[[Category: Narasimhan P]]	+	[[Category: Grondine, M]]
-	[[Category: Robb G]]	+	[[Category: Narasimhan, P]]
-	[[Category: Schimpl M]]	+	[[Category: Robb, G]]
-	[[Category: Scott JS]]	+	[[Category: Schimpl, M]]
-	[[Category: Stubbs C]]	+	[[Category: Scott, J S]]
-	[[Category: Tentarelli S]]	+	[[Category: Stubbs, C]]
-	[[Category: Underwood E]]	+	[[Category: Tentarelli, S]]
-	[[Category: Vazquez-Chantada M]]	+	[[Category: Underwood, E]]
-	[[Category: Wagner DJ]]	+	[[Category: Vazquez-Chantada, M]]
		+	[[Category: Wagner, D J]]
		+	[[Category: Allosteric inhibitor]]
		+	[[Category: Fragment-based drug design]]
		+	[[Category: Oncology]]
		+	[[Category: Synthetic lethal therapy]]
		+	[[Category: Transferase]]

OCA at 08:21, 21 April 2021

2021-04-21T08:21:48Z

←Older revision		Revision as of 08:21, 21 April 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7bht is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of MAT2a with quinazolinone fragment 5 bound in the allosteric site==
-		+	<StructureSection load='7bht' size='340' side='right'caption='[[7bht]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHT FirstGlance]. <br>
-	~~Description~~:	+	</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=7bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bht OCA], [https://pdbe.org/7bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bht RCSB], [https://www.ebi.ac.uk/pdbsum/7bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bht ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Argyrou A]]
		+	[[Category: Bagal S]]
		+	[[Category: Borjesson U]]
		+	[[Category: Cheung T]]
		+	[[Category: Chiarparin E]]
		+	[[Category: Collie I]]
		+	[[Category: De Fusco C]]
		+	[[Category: Evans L]]
		+	[[Category: Grondine M]]
		+	[[Category: Narasimhan P]]
		+	[[Category: Robb G]]
		+	[[Category: Schimpl M]]
		+	[[Category: Scott JS]]
		+	[[Category: Stubbs C]]
		+	[[Category: Tentarelli S]]
		+	[[Category: Underwood E]]
		+	[[Category: Vazquez-Chantada M]]
		+	[[Category: Wagner DJ]]

OCA at 05:25, 24 February 2021

2021-02-24T05:25:24Z

←Older revision		Revision as of 05:25, 24 February 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7bht is ON HOLD	+	The entry 7bht is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7bht" [edit=sysop:move=sysop]

2021-01-20T06:40:47Z

Protected "7bht" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:40, 20 January 2021

OCA: New page: '''Unreleased structure''' The entry 7bht is ON HOLD Authors: Description: Category: Unreleased Structures

2021-01-20T06:40:46Z

New page: '''Unreleased structure''' The entry 7bht is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7bht is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]