8gyd - Revision history

OCA at 16:12, 14 March 2024

OCA — Thu, 14 Mar 2024 16:12:47 GMT

←Older revision		Revision as of 16:12, 14 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/GST26_SCHJA GST26_SCHJA] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. GST isoenzymes appear to play a central role in the parasite detoxification system. Other functions are also suspected including a role in increasing the solubility of haematin in the parasite gut.		[https://www.uniprot.org/uniprot/GST26_SCHJA GST26_SCHJA] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. GST isoenzymes appear to play a central role in the parasite detoxification system. Other functions are also suspected including a role in increasing the solubility of haematin in the parasite gut.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The DNA-encoded library (DEL) is a powerful hit-generation tool in drug discovery. This study describes a new DEL with a privileged scaffold quinazolin-4(3H)-one developed by a robust DNA-compatible multicomponent reaction and a series of novel glutathione S-transferase (GST) inhibitors that were identified through affinity-mediated DEL selection. A novel inhibitor 16 was subsequently verified with an inhibitory potency value of 1.55 +/- 0.02 muM against SjGST and 2.02 +/- 0.20 muM against hGSTM2. Further optimization was carried out via various structure-activity relationship studies. And especially, the co-crystal structure of the compound 16 with the SjGST was unveiled, which clearly demonstrated its binding mode was quite different from the known GSH-like compounds. This new type of probe is likely to play a different role compared with the GSH, which may provide new opportunities to discover more potent GST inhibitors.
-
-	Discovery, SAR Study of GST Inhibitors from a Novel Quinazolin-4(1H)-one Focused DNA-Encoded Library.,Wen X, Zhang M, Duan Z, Suo Y, Lu W, Jin R, Mu B, Li K, Zhang X, Meng L, Hong Y, Wang X, Hu H, Zhu J, Song W, Shen A, Lu X J Med Chem. 2023 Aug 8. doi: 10.1021/acs.jmedchem.2c02129. PMID:37552553<ref>PMID:37552553</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8gyd" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 05:54, 23 August 2023

OCA — Wed, 23 Aug 2023 05:54:04 GMT

←Older revision		Revision as of 05:54, 23 August 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8gyd is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of Schistosoma japonicum Glutathione S-transferase bound with the ligand complex of 16==
		+	<StructureSection load='8gyd' size='340' side='right'caption='[[8gyd]], [[Resolution\|resolution]] 1.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8gyd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_japonicum Schistosoma japonicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GYD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GYD FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0IH:(2R)-2-[[2-(5-chloranylthiophen-2-yl)-4-oxidanylidene-6-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]quinazolin-3-yl]methyl]-3-(4-chlorophenyl)propanoic+acid'>0IH</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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=8gyd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gyd OCA], [https://pdbe.org/8gyd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gyd RCSB], [https://www.ebi.ac.uk/pdbsum/8gyd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gyd ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GST26_SCHJA GST26_SCHJA] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. GST isoenzymes appear to play a central role in the parasite detoxification system. Other functions are also suspected including a role in increasing the solubility of haematin in the parasite gut.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The DNA-encoded library (DEL) is a powerful hit-generation tool in drug discovery. This study describes a new DEL with a privileged scaffold quinazolin-4(3H)-one developed by a robust DNA-compatible multicomponent reaction and a series of novel glutathione S-transferase (GST) inhibitors that were identified through affinity-mediated DEL selection. A novel inhibitor 16 was subsequently verified with an inhibitory potency value of 1.55 +/- 0.02 muM against SjGST and 2.02 +/- 0.20 muM against hGSTM2. Further optimization was carried out via various structure-activity relationship studies. And especially, the co-crystal structure of the compound 16 with the SjGST was unveiled, which clearly demonstrated its binding mode was quite different from the known GSH-like compounds. This new type of probe is likely to play a different role compared with the GSH, which may provide new opportunities to discover more potent GST inhibitors.

-	~~Authors~~:	+	Discovery, SAR Study of GST Inhibitors from a Novel Quinazolin-4(1H)-one Focused DNA-Encoded Library.,Wen X, Zhang M, Duan Z, Suo Y, Lu W, Jin R, Mu B, Li K, Zhang X, Meng L, Hong Y, Wang X, Hu H, Zhu J, Song W, Shen A, Lu X J Med Chem. 2023 Aug 8. doi: 10.1021/acs.jmedchem.2c02129. PMID:37552553<ref>PMID:37552553</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8gyd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Schistosoma japonicum]]
		+	[[Category: Hu H]]
		+	[[Category: Jin R]]
		+	[[Category: Lu X]]
		+	[[Category: Song W]]
		+	[[Category: Wen X]]
		+	[[Category: Zhu J]]

OCA at 04:11, 26 October 2022

OCA — Wed, 26 Oct 2022 04:11:21 GMT

←Older revision		Revision as of 04:11, 26 October 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8gyd is ON HOLD	+	The entry 8gyd is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8gyd" [edit=sysop:move=sysop]

OCA — Wed, 28 Sep 2022 04:54:30 GMT

Protected "8gyd" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:54, 28 September 2022

OCA: New page: '''Unreleased structure''' The entry 8gyd is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 28 Sep 2022 04:54:29 GMT

New page: '''Unreleased structure''' The entry 8gyd is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8gyd is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]