OCA at 11:43, 1 February 2024

OCA — Thu, 01 Feb 2024 11:43:51 GMT

←Older revision		Revision as of 11:43, 1 February 2024
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8pl5 is ~~ON HOLD until Paper~~ Publication	+	==Thioredoxin glutathione reductase of Schistosoma mansoni fragment screen hit 6.==
		+	<StructureSection load='8pl5' size='340' side='right'caption='[[8pl5]], [[Resolution\|resolution]] 2.15Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8pl5]] is a 2 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=8PL5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PL5 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]] 2.15Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=ZM8:1-[4-(cyclopropylamino)piperidin-1-yl]ethanone'>ZM8</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=8pl5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pl5 OCA], [https://pdbe.org/8pl5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pl5 RCSB], [https://www.ebi.ac.uk/pdbsum/8pl5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pl5 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q962Y6_SCHMA Q962Y6_SCHMA]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Schistosomiasis is caused by parasites of the genus Schistosoma, which infect more than 200 million people. Praziquantel (PZQ) has been the main drug for controlling schistosomiasis for over four decades, but despite that it is ineffective against juvenile worms and size and taste issues with its pharmaceutical forms impose challenges for treating school-aged children. It is also important to note that PZQ resistant strains can be generated in laboratory conditions and observed in the field, hence its extensive use in mass drug administration programs raises concerns about resistance, highlighting the need to search for new schistosomicidal drugs. Schistosomes survival relies on the redox enzyme thioredoxin glutathione reductase (TGR), a validated target for the development of new anti-schistosomal drugs. Here we report a high-throughput fragment screening campaign of 768 compounds against S. mansoni TGR (SmTGR) using X-ray crystallography. We observed 49 binding events involving 35 distinct molecular fragments which were found to be distributed across 16 binding sites. Most sites are described for the first time within SmTGR, a noteworthy exception being the "doorstop pocket" near the NADPH binding site. We have compared results from hotspots and pocket druggability analysis of SmTGR with the experimental binding sites found in this work, with our results indicating only limited coincidence between experimental and computational results. Finally, we discuss that binding sites at the doorstop/NADPH binding site and in the SmTGR dimer interface, should be prioritized for developing SmTGR inhibitors as new antischistosomal drugs.

-	~~Authors: Ribeiro, L~~., Montoya, ~~B.O., Moreira~~-~~Filho~~, ~~J.T.~~, Bowyer, S., ~~Verma~~, A., Neves, ~~B.J.~~, Owens, ~~R.J., Andrade, C.H.~~, Silva-Jr~~, F~~.P.~~, Furnham, N~~.	+	Fragment library screening by X-ray crystallography and binding site analysis on thioredoxin glutathione reductase of Schistosoma mansoni.,de Souza Neto LR, Montoya BO, Brandao-Neto J, Verma A, Bowyer S, Moreira-Filho JT, Dantas RF, Neves BJ, Andrade CH, von Delft F, Owens RJ, Furnham N, Silva-Jr FP Sci Rep. 2024 Jan 18;14(1):1582. doi: 10.1038/s41598-024-52018-2. PMID:38238498<ref>PMID:38238498</ref>

-	~~Description: Thioredoxin glutathione reductase~~ of ~~Schistosoma mansoni fragment screen hit 6~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Silva-Jr, F.P~~]]	+	<div class="pdbe-citations 8pl5" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Neves, B.J~~]]	+	== References ==
-	[[Category: ~~Andrade, C.H~~]]	+	<references/>
-	[[Category: Furnham, N]]	+	__TOC__
-	[[Category: ~~Owens, R.J~~]]	+	</StructureSection>
-	[[Category: ~~Ribeiro, L~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Verma, A~~]]	+	[[Category: Schistosoma mansoni]]
-	[[Category: ~~Bowyer, S~~]]	+	[[Category: Andrade CH]]
-	[[Category: ~~Moreira~~-~~Filho, J.T~~]]	+	[[Category: Bowyer S]]
-	[[Category: ~~Montoya, B.O~~]]	+	[[Category: Furnham N]]
		+	[[Category: Montoya BO]]
		+	[[Category: Moreira-Filho JT]]
		+	[[Category: Neves BJ]]
		+	[[Category: Owens RJ]]
		+	[[Category: Ribeiro L]]
		+	[[Category: Silva-Jr FP]]
		+	[[Category: Verma A]]

OCA at 09:04, 2 August 2023

OCA — Wed, 02 Aug 2023 09:04:16 GMT

←Older revision		Revision as of 09:04, 2 August 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8pl5 is ON HOLD	+	The entry 8pl5 is ON HOLD until Paper Publication

	Authors: Ribeiro, L., Montoya, B.O., Moreira-Filho, J.T., Bowyer, S., Verma, A., Neves, B.J., Owens, R.J., Andrade, C.H., Silva-Jr, F.P., Furnham, N.		Authors: Ribeiro, L., Montoya, B.O., Moreira-Filho, J.T., Bowyer, S., Verma, A., Neves, B.J., Owens, R.J., Andrade, C.H., Silva-Jr, F.P., Furnham, N.

OCA: Protected "8pl5" [edit=sysop:move=sysop]

OCA — Wed, 05 Jul 2023 04:17:13 GMT

Protected "8pl5" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:17, 5 July 2023

OCA: New page: '''Unreleased structure''' The entry 8pl5 is ON HOLD Authors: Ribeiro, L., Montoya, B.O., Moreira-Filho, J.T., Bowyer, S., Verma, A., Neves, B.J., Owens, R.J., Andrade, C.H., Silva-Jr, ...

OCA — Wed, 05 Jul 2023 04:17:11 GMT

New page: '''Unreleased structure''' The entry 8pl5 is ON HOLD Authors: Ribeiro, L., Montoya, B.O., Moreira-Filho, J.T., Bowyer, S., Verma, A., Neves, B.J., Owens, R.J., Andrade, C.H., Silva-Jr, ...

New page

'''Unreleased structure'''

The entry 8pl5 is ON HOLD

Authors: Ribeiro, L., Montoya, B.O., Moreira-Filho, J.T., Bowyer, S., Verma, A., Neves, B.J., Owens, R.J., Andrade, C.H., Silva-Jr, F.P., Furnham, N.

Description: Thioredoxin glutathione reductase of Schistosoma mansoni fragment screen hit 6.
[[Category: Unreleased Structures]]
[[Category: Silva-Jr, F.P]]
[[Category: Neves, B.J]]
[[Category: Andrade, C.H]]
[[Category: Furnham, N]]
[[Category: Owens, R.J]]
[[Category: Ribeiro, L]]
[[Category: Verma, A]]
[[Category: Bowyer, S]]
[[Category: Moreira-Filho, J.T]]
[[Category: Montoya, B.O]]

8pl5 - Revision history

OCA at 11:43, 1 February 2024

OCA at 09:04, 2 August 2023

OCA: Protected "8pl5" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8pl5 is ON HOLD Authors: Ribeiro, L., Montoya, B.O., Moreira-Filho, J.T., Bowyer, S., Verma, A., Neves, B.J., Owens, R.J., Andrade, C.H., Silva-Jr, ...