OCA at 12:54, 1 February 2024

OCA — Thu, 01 Feb 2024 12:54:11 GMT

←Older revision		Revision as of 12:54, 1 February 2024
Line 1:		Line 1:

	==Trypanosoma brucei PTR1 (TbPTR1) in complex with pyrimethamine==		==Trypanosoma brucei PTR1 (TbPTR1) in complex with pyrimethamine==
-	<StructureSection load='7opj' size='340' side='right'caption='[[7opj]]' scene=''>	+	<StructureSection load='7opj' size='340' side='right'caption='[[7opj]], [[Resolution\|resolution]] 1.34Å' 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=7OPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7opj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPJ 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=7opj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7opj OCA], [https://pdbe.org/7opj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7opj RCSB], [https://www.ebi.ac.uk/pdbsum/7opj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7opj 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]] 1.34Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=7opj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7opj OCA], [https://pdbe.org/7opj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7opj RCSB], [https://www.ebi.ac.uk/pdbsum/7opj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7opj ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/O76290_TRYBB O76290_TRYBB]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Trypanosoma and Leishmania parasites are the etiological agents of various threatening neglected tropical diseases (NTDs), including human African trypanosomiasis (HAT), Chagas disease, and various types of leishmaniasis. Recently, meaningful progresses in the treatment of HAT, due to Trypanosoma brucei (Tb), have been achieved by the introduction of fexinidazole and the combination therapy eflornithine-nifurtimox. Nevertheless, due to drug resistance issues and the exitance of animal reservoirs, the development of new NTD treatments is still required. For this purpose, we explored the combined targeting of two key folate enzymes, dihydrofolate reductase (DHFR) and pteridine reductase 1 (PTR1). We formerly showed that the TbDHFR inhibitor cycloguanil (CYC) also targets TbPTR1, although with reduced affinity. Here, we explored a small library of CYC analogues to understand how their substitution pattern affects the inhibition of both TbPTR1 and TbDHFR. Some novel structural features responsible for an improved, but preferential, ability of CYC analogues to target TbPTR1 were disclosed. Furthermore, we showed that the known drug pyrimethamine (PYR) effectively targets both enzymes, also unveiling its binding mode to TbPTR1. The structural comparison between PYR and CYC binding modes to TbPTR1 and TbDHFR provided key insights for the future design of dual inhibitors for HAT therapy.
		+
		+	Evidence of Pyrimethamine and Cycloguanil Analogues as Dual Inhibitors of Trypanosoma brucei Pteridine Reductase and Dihydrofolate Reductase.,Tassone G, Landi G, Linciano P, Francesconi V, Tonelli M, Tagliazucchi L, Costi MP, Mangani S, Pozzi C Pharmaceuticals (Basel). 2021 Jun 30;14(7). pii: ph14070636. doi:, 10.3390/ph14070636. PMID:34209148<ref>PMID:34209148</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7opj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Pteridine reductase\|Pteridine reductase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Trypanosoma brucei brucei]]
	[[Category: Landi G]]		[[Category: Landi G]]
	[[Category: Mangani S]]		[[Category: Mangani S]]
	[[Category: Pozzi C]]		[[Category: Pozzi C]]
	[[Category: Tassone G]]		[[Category: Tassone G]]

OCA at 09:55, 14 July 2021

OCA — Wed, 14 Jul 2021 09:55:59 GMT

←Older revision		Revision as of 09:55, 14 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7opj ~~is ON HOLD until Paper Publication~~	+	==Trypanosoma brucei PTR1 (TbPTR1) in complex with pyrimethamine==
-		+	<StructureSection load='7opj' size='340' side='right'caption='[[7opj]]' scene=''>
-	~~Authors~~: ~~Tassone~~, G., ~~Landi~~, G., ~~Pozzi, C~~., ~~Mangani, S~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPJ FirstGlance]. <br>
-	~~Description: Trypanosoma brucei PTR1 (TbPTR1) in complex with pyrimethamine~~	+	</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=7opj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7opj OCA], [https://pdbe.org/7opj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7opj RCSB], [https://www.ebi.ac.uk/pdbsum/7opj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7opj ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Landi, G]]	+	__TOC__
-	[[Category: ~~Tassone, G~~]]	+	</StructureSection>
-	[[Category: ~~Mangani, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Pozzi, C~~]]	+	[[Category: Landi G]]
		+	[[Category: Mangani S]]
		+	[[Category: Pozzi C]]
		+	[[Category: Tassone G]]

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

OCA — Wed, 09 Jun 2021 11:14:42 GMT

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

←Older revision

Revision as of 11:14, 9 June 2021

OCA: New page: '''Unreleased structure''' The entry 7opj is ON HOLD until Paper Publication Authors: Tassone, G., Landi, G., Pozzi, C., Mangani, S. Description: Trypanosoma brucei PTR1 (TbPTR1) in co...

OCA — Wed, 09 Jun 2021 11:14:41 GMT

New page: '''Unreleased structure''' The entry 7opj is ON HOLD until Paper Publication Authors: Tassone, G., Landi, G., Pozzi, C., Mangani, S. Description: Trypanosoma brucei PTR1 (TbPTR1) in co...

New page

'''Unreleased structure'''

The entry 7opj is ON HOLD until Paper Publication

Authors: Tassone, G., Landi, G., Pozzi, C., Mangani, S.

Description: Trypanosoma brucei PTR1 (TbPTR1) in complex with pyrimethamine
[[Category: Unreleased Structures]]
[[Category: Landi, G]]
[[Category: Tassone, G]]
[[Category: Mangani, S]]
[[Category: Pozzi, C]]

7opj - Revision history

OCA at 12:54, 1 February 2024

OCA at 09:55, 14 July 2021

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

OCA: New page: '''Unreleased structure''' The entry 7opj is ON HOLD until Paper Publication Authors: Tassone, G., Landi, G., Pozzi, C., Mangani, S. Description: Trypanosoma brucei PTR1 (TbPTR1) in co...