7p2u - Revision history

OCA at 13:00, 1 February 2024

OCA — Thu, 01 Feb 2024 13:00:37 GMT

←Older revision		Revision as of 13:00, 1 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7p2u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2U FirstGlance]. <br>		<table><tr><td colspan='2'>[[7p2u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4WB:5-[[(2R)-2-(3-chlorophenyl)-1-methyl-spiro[2H-indole-3,4-piperidine]-1-yl]methyl]-N-oxidanyl-thiophene-2-carboxamide'>4WB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4WB:5-[[(2R)-2-(3-chlorophenyl)-1-methyl-spiro[2H-indole-3,4-piperidine]-1-yl]methyl]-N-oxidanyl-thiophene-2-carboxamide'>4WB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7p2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2u OCA], [https://pdbe.org/7p2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2u RCSB], [https://www.ebi.ac.uk/pdbsum/7p2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2u 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=7p2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2u OCA], [https://pdbe.org/7p2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2u RCSB], [https://www.ebi.ac.uk/pdbsum/7p2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2u ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/A5H660_SCHMA A5H660_SCHMA]]	+	[https://www.uniprot.org/uniprot/A5H660_SCHMA A5H660_SCHMA]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7p2u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7p2u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone deacetylase 3D structures\|Histone deacetylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:45, 7 September 2022

OCA — Wed, 07 Sep 2022 19:45:56 GMT

←Older revision		Revision as of 19:45, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='7p2u' size='340' side='right'caption='[[7p2u]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='7p2u' size='340' side='right'caption='[[7p2u]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7p2u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7p2u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2U FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4WB:5-[[(2R)-2-(3-chlorophenyl)-1-methyl-spiro[2H-indole-3,4-piperidine]-1-yl]methyl]-N-oxidanyl-thiophene-2-carboxamide'>4WB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4WB:5-[[(2R)-2-(3-chlorophenyl)-1-methyl-spiro[2H-indole-3,4-piperidine]-1-yl]methyl]-N-oxidanyl-thiophene-2-carboxamide'>4WB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7p2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2u OCA], [https://pdbe.org/7p2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2u RCSB], [https://www.ebi.ac.uk/pdbsum/7p2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2u 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=7p2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2u OCA], [https://pdbe.org/7p2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2u RCSB], [https://www.ebi.ac.uk/pdbsum/7p2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2u ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/A5H660_SCHMA A5H660_SCHMA]]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Campiani, G]]	+	[[Category: Schistosoma mansoni]]
-	[[Category: Gemma, S]]	+	[[Category: Campiani G]]
-	[[Category: Ruberti, G]]	+	[[Category: Gemma S]]
-	[[Category: Saccoccia, F]]	+	[[Category: Ruberti G]]
-	~~[[Category: Hdaci]]~~	+	[[Category: Saccoccia F]]
-	~~[[Category: Histone-deacetilase inhibitor complex]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Novel binding-site]]~~	+
-	~~[[Category: Smhdac8~~]]	+

OCA at 06:42, 31 August 2022

OCA — Wed, 31 Aug 2022 06:42:55 GMT

←Older revision		Revision as of 06:42, 31 August 2022
Line 1:		Line 1:

	==Crystal structure of Schistosoma mansoni HDAC8 in complex with a 3-chlorophenyl-spiroindoline capped hydroxamate-based inhibitor, bound to a novel site==		==Crystal structure of Schistosoma mansoni HDAC8 in complex with a 3-chlorophenyl-spiroindoline capped hydroxamate-based inhibitor, bound to a novel site==
-	<StructureSection load='7p2u' size='340' side='right'caption='[[7p2u]]' scene=''>	+	<StructureSection load='7p2u' size='340' side='right'caption='[[7p2u]], [[Resolution\|resolution]] 1.80Å' 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=7P2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7p2u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2U 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=7p2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2u OCA], [https://pdbe.org/7p2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2u RCSB], [https://www.ebi.ac.uk/pdbsum/7p2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2u 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=4WB:5-[[(2R)-2-(3-chlorophenyl)-1-methyl-spiro[2H-indole-3,4-piperidine]-1-yl]methyl]-N-oxidanyl-thiophene-2-carboxamide'>4WB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7p2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2u OCA], [https://pdbe.org/7p2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2u RCSB], [https://www.ebi.ac.uk/pdbsum/7p2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2u ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Parasitic diseases cause significant global morbidity and mortality particularly in the poorest regions of the world. Schistosomiasis, one of the most widespread neglected tropical diseases, affects more than 200 million people worldwide. Histone deacetylase (HDAC) inhibitors are prominent epigenetic drugs that are being investigated in the treatment of several diseases, including cancers and parasitic diseases. Schistosoma mansoni HDAC8 (SmHDAC8) is highly expressed in all life cycle stages of the parasite and selective inhibition is required in order to avoid undesirable off-target effects in the host. Herein, by X-ray crystal structures of SmHDAC8-inhibitor complexes, biochemical and phenotypic studies, we found two schistosomicidal spiroindoline-derivatives binding a novel site, next to Trp198, on the enzyme surface. We determined that by acting on this site, either by mutation of the Trp198 or by compound binding, a decrease in the activity of the enzyme is achieved. Remarkably, this allosteric site differs from the human counterpart; rather, it is conserved in all Schistosoma spp., as well as Rhabidoptera and Trematoda classes, thus paving the way for the design of HDAC8-selective allosteric inhibitors with improved properties.
		+
		+	Crystal structures of Schistosoma mansoni histone deacetylase 8 reveal a novel binding site for allosteric inhibitors.,Saccoccia F, Pozzetti L, Gimmelli R, Butini S, Guidi A, Papoff G, Giannaccari M, Brogi S, Scognamiglio V, Gemma S, Ruberti G, Campiani G J Biol Chem. 2022 Aug 12:102375. doi: 10.1016/j.jbc.2022.102375. PMID:35970392<ref>PMID:35970392</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7p2u" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Campiani G]]	+	[[Category: Campiani, G]]
-	[[Category: Gemma S]]	+	[[Category: Gemma, S]]
-	[[Category: Ruberti G]]	+	[[Category: Ruberti, G]]
-	[[Category: Saccoccia F]]	+	[[Category: Saccoccia, F]]
		+	[[Category: Hdaci]]
		+	[[Category: Histone-deacetilase inhibitor complex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Novel binding-site]]
		+	[[Category: Smhdac8]]

OCA at 06:48, 20 July 2022

OCA — Wed, 20 Jul 2022 06:48:43 GMT

←Older revision		Revision as of 06:48, 20 July 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7p2u is ON HOLD until Paper Publication~~	+	==Crystal structure of Schistosoma mansoni HDAC8 in complex with a 3-chlorophenyl-spiroindoline capped hydroxamate-based inhibitor, bound to a novel site==
-		+	<StructureSection load='7p2u' size='340' side='right'caption='[[7p2u]]' scene=''>
-	~~Authors: Saccoccia, F., Gemma, S., Campiani, G., Ruberti, G.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2U FirstGlance]. <br>
-	~~Description:~~ Crystal structure of Schistosoma mansoni HDAC8 in complex with a 3-chlorophenyl-spiroindoline capped hydroxamate-based inhibitor, bound to a novel site	+	</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=7p2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2u OCA], [https://pdbe.org/7p2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2u RCSB], [https://www.ebi.ac.uk/pdbsum/7p2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2u ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Ruberti~~, G]]	+	__TOC__
-	[[Category: ~~Saccoccia, F~~]]	+	</StructureSection>
-	[[Category: Campiani, G]]	+	[[Category: Large Structures]]
-	[[Category: Gemma, S]]	+	[[Category: Campiani G]]
		+	[[Category: Gemma S]]
		+	[[Category: Ruberti G]]
		+	[[Category: Saccoccia F]]

OCA at 09:28, 28 July 2021

OCA — Wed, 28 Jul 2021 09:28:17 GMT

←Older revision		Revision as of 09:28, 28 July 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7p2u is ON HOLD	+	The entry 7p2u is ON HOLD until Paper Publication

	Authors: Saccoccia, F., Gemma, S., Campiani, G., Ruberti, G.		Authors: Saccoccia, F., Gemma, S., Campiani, G., Ruberti, G.

OCA: Protected "7p2u" [edit=sysop:move=sysop]

OCA — Wed, 14 Jul 2021 08:52:17 GMT

Protected "7p2u" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:52, 14 July 2021

OCA: New page: '''Unreleased structure''' The entry 7p2u is ON HOLD Authors: Saccoccia, F., Gemma, S., Campiani, G., Ruberti, G. Description: Crystal structure of Schistosoma mansoni HDAC8 in complex...

OCA — Wed, 14 Jul 2021 08:52:16 GMT

New page: '''Unreleased structure''' The entry 7p2u is ON HOLD Authors: Saccoccia, F., Gemma, S., Campiani, G., Ruberti, G. Description: Crystal structure of Schistosoma mansoni HDAC8 in complex...

New page

'''Unreleased structure'''

The entry 7p2u is ON HOLD

Authors: Saccoccia, F., Gemma, S., Campiani, G., Ruberti, G.

Description: Crystal structure of Schistosoma mansoni HDAC8 in complex with a 3-chlorophenyl-spiroindoline capped hydroxamate-based inhibitor, bound to a novel site
[[Category: Unreleased Structures]]
[[Category: Ruberti, G]]
[[Category: Saccoccia, F]]
[[Category: Campiani, G]]
[[Category: Gemma, S]]