6gcq - Revision history

OCA at 06:49, 17 April 2019

OCA — Wed, 17 Apr 2019 06:49:28 GMT

←Older revision		Revision as of 06:49, 17 April 2019
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	<StructureSection load='6gcq' size='340' side='right'caption='[[6gcq]], [[Resolution\|resolution]] 1.58Å' scene=''>		<StructureSection load='6gcq' size='340' side='right'caption='[[6gcq]], [[Resolution\|resolution]] 1.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gcq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GCQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GCQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gcq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybb Trybb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GCQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GCQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EUH:6-(trifluoromethylsulfanyl)-1,3-benzothiazol-2-amine'>EUH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EUH:6-(trifluoromethylsulfanyl)-1,3-benzothiazol-2-amine'>EUH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6gck\|6gck]], [[6gcl\|6gcl]], [[6gcp\|6gcp]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6gck\|6gck]], [[6gcl\|6gcl]], [[6gcp\|6gcp]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5702 TRYBB])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gcq OCA], [http://pdbe.org/6gcq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gcq RCSB], [http://www.ebi.ac.uk/pdbsum/6gcq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gcq ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gcq OCA], [http://pdbe.org/6gcq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gcq RCSB], [http://www.ebi.ac.uk/pdbsum/6gcq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gcq ProSAT]</span></td></tr>
	</table>		</table>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Trybb]]
	[[Category: Landi, G]]		[[Category: Landi, G]]
	[[Category: Mangani, S]]		[[Category: Mangani, S]]

OCA at 06:55, 3 April 2019

OCA — Wed, 03 Apr 2019 06:55:52 GMT

←Older revision		Revision as of 06:55, 3 April 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6gcq is ~~ON HOLD until Paper~~ Publication	+	==Trypanosoma brucei PTR1 in complex with inhibitor 2b (F192)==
		+	<StructureSection load='6gcq' size='340' side='right'caption='[[6gcq]], [[Resolution\|resolution]] 1.58Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6gcq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GCQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GCQ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EUH:6-(trifluoromethylsulfanyl)-1,3-benzothiazol-2-amine'>EUH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6gck\|6gck]], [[6gcl\|6gcl]], [[6gcp\|6gcp]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gcq OCA], [http://pdbe.org/6gcq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gcq RCSB], [http://www.ebi.ac.uk/pdbsum/6gcq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gcq ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	2-amino-benzo[d]thiazole has been identified as new core moiety for the development of improved PTR1 inhibitors and anti-Trypanosomatidic agents. Through a molecular docking approach and the crystal structure of 6-(methylsulfonyl)benzo[d]thiazol-2-amine ternary complex with TbPTR1, 42 new compounds were designed, synthesized and evaluated for their ability to inhibit T. brucei and L. major PTR1 enzymes and in-vitro activity against Trypanosoma brucei and amastigote stage of Leishmania infantum. We identified several 2-amino-benzo[d]thiazole derivatives with improved activity against the enzymes (TbPTR1 IC50 = 0.35 microM; LmPTR1 IC50 = 1.9 microM) and anti-parasitic activity against T. brucei in the low microM range. Ten compounds, with low/sub micromolar inhibitor activity against TbPTR1, were able to potentiate the antiparasitic activity of methotrexate (MTX) when evaluated in combination against T. brucei, with a Potentiating Index (PI) ranging between 1.2 and 2.7. The compound library was profile for an early ADME-Toxicity profile and the compounds showing the best in vitro/enzymatic inhibition properties were selected for progression. 2-amino-N-benzylbenzo[d]thiazole-6-carboxamide (4c), was finally identified as a novel potent and selective anti-trypanocydal agent (EC50 = 7.0 microM) with an overall safe early ADME-Toxicity profile. The pharmacokinetic studies of 4c in BALB/c mice using a hydroxypropyl-beta-cyclodextrin formulation yielded good oral bioavailability, confirming its suitability for progression to in-vivo anti-parasitic studies.

-	~~Authors: Pozzi~~, C., Landi, G., ~~Mangani~~, S.	+	Enhancement of benzothiazoles as Pteridine Reductase-1 (PTR1) inhibitors for the treatment of Trypanosomatidic infections.,Linciano P, Pozzi C, Dello Iacono L, di PIsa F, Landi G, Bonucci A, Gul S, Kuzikov M, Ellinger B, Witt G, Santarem N, Baptista C, Franco C, Borsoi Moraes C, Muller W, Wittig U, Luciani R, Sesenna A, Quotadamo A, Ferrari S, Pohner I, Cordeiro-da-Silva A, Mangani S, Costantino L, Costi MP J Med Chem. 2019 Mar 25. doi: 10.1021/acs.jmedchem.8b02021. PMID:30908048<ref>PMID:30908048</ref>

-	~~Description~~: ~~Trypanosoma brucei PTR1 in complex with inhibitor 2b (F192)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6gcq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Landi, G]]		[[Category: Landi, G]]
-	[[Category: Pozzi, C]]
	[[Category: Mangani, S]]		[[Category: Mangani, S]]
		+	[[Category: Pozzi, C]]
		+	[[Category: Benzothiazole]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Pteridine reductase]]
		+	[[Category: Ptr1]]
		+	[[Category: Tbptr1]]
		+	[[Category: Trypanosoma brucei]]

OCA at 04:11, 16 May 2018

OCA — Wed, 16 May 2018 04:11:27 GMT

←Older revision		Revision as of 04:11, 16 May 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6gcq is ON HOLD	+	The entry 6gcq is ON HOLD until Paper Publication

	Authors: Pozzi, C., Landi, G., Mangani, S.		Authors: Pozzi, C., Landi, G., Mangani, S.
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Landi, G]]		[[Category: Landi, G]]
-	[[Category: Mangani, S]]
	[[Category: Pozzi, C]]		[[Category: Pozzi, C]]
		+	[[Category: Mangani, S]]

OCA: Protected "6gcq" [edit=sysop:move=sysop]

OCA — Wed, 25 Apr 2018 04:23:06 GMT

Protected "6gcq" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:23, 25 April 2018

OCA: New page: '''Unreleased structure''' The entry 6gcq is ON HOLD Authors: Pozzi, C., Landi, G., Mangani, S. Description: Trypanosoma brucei PTR1 in complex with inhibitor 2b (F192) [[Category: Unr...

OCA — Wed, 25 Apr 2018 04:23:04 GMT

New page: '''Unreleased structure''' The entry 6gcq is ON HOLD Authors: Pozzi, C., Landi, G., Mangani, S. Description: Trypanosoma brucei PTR1 in complex with inhibitor 2b (F192) [[Category: Unr...

New page

'''Unreleased structure'''

The entry 6gcq is ON HOLD

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

Description: Trypanosoma brucei PTR1 in complex with inhibitor 2b (F192)
[[Category: Unreleased Structures]]
[[Category: Landi, G]]
[[Category: Mangani, S]]
[[Category: Pozzi, C]]