5j5a - Revision history

OCA at 12:36, 6 March 2024

OCA — Wed, 06 Mar 2024 12:36:38 GMT

←Older revision		Revision as of 12:36, 6 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/Q38C91_TRYB2 Q38C91_TRYB2]		[https://www.uniprot.org/uniprot/Q38C91_TRYB2 Q38C91_TRYB2]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	A screening hit 1 against Trypanosoma brucei methionyl-tRNA synthetase was optimized using a structure-guided approach. The optimization led to the identification of two novel series of potent inhibitors, the cyclic linker and linear linker series. Compounds of both series were potent in a T. brucei growth inhibition assay while showing low toxicity to mammalian cells. The best compound of each series, 16 and 31, exhibited EC50s of 39 and 22 nM, respectively. Compounds 16 and 31 also exhibited promising PK properties after oral dosing in mice. Moreover, compound 31 had moderately good brain permeability, with a brain/plasma ratio of 0.27 at 60 min after IP injection. This study provides new lead compounds for arriving at new treatments of human African trypanosomiasis (HAT).
-
-	Structure-guided design of novel Trypanosoma brucei Methionyl-tRNA synthetase inhibitors.,Huang W, Zhang Z, Barros-Alvarez X, Koh CY, Ranade RM, Gillespie JR, Creason SA, Shibata S, Verlinde CL, Hol WG, Buckner FS, Fan E Eur J Med Chem. 2016 Nov 29;124:1081-1092. doi: 10.1016/j.ejmech.2016.10.024., Epub 2016 Oct 14. PMID:27788467<ref>PMID:27788467</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5j5a" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 10:48, 6 September 2023

OCA — Wed, 06 Sep 2023 10:48:53 GMT

←Older revision		Revision as of 10:48, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='5j5a' size='340' side='right'caption='[[5j5a]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='5j5a' size='340' side='right'caption='[[5j5a]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j5a]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Tryb2 Tryb2~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5J5A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j5a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J5A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=756:[(3S)-3-(1H-BENZIMIDAZOL-2-YL)PIPERIDIN-1-YL](2-METHYL-1-BENZOFURAN-5-YL)METHANONE'>756</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</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]] 2.7Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb10.70.6470 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=185431 TRYB2])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=756:[(3S)-3-(1H-BENZIMIDAZOL-2-YL)PIPERIDIN-1-YL](2-METHYL-1-BENZOFURAN-5-YL)METHANONE'>756</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </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=5j5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5a OCA], [https://pdbe.org/5j5a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j5a RCSB], [https://www.ebi.ac.uk/pdbsum/5j5a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5a ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5j5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5a OCA], [~~http~~://pdbe.org/5j5a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5j5a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5j5a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5a ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q38C91_TRYB2 Q38C91_TRYB2]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Methionine--tRNA ligase]]~~	+	[[Category: Trypanosoma brucei brucei TREU927]]
-	~~[[Category: Tryb2~~]]	+	[[Category: Barros-Alvarez X]]
-	[[Category: Barros-Alvarez, X]]	+	[[Category: Hol WGJ]]
-	[[Category: Hol~~, W G.J~~]]	+	[[Category: Koh CY]]
-	[[Category: Koh~~, C Y]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Ligase-ligase inhibitor complex]]~~	+
-	~~[[Category: Methionine]]~~	+
-	~~[[Category: Synthetase~~]]	+

OCA at 07:30, 10 June 2020

OCA — Wed, 10 Jun 2020 07:30:20 GMT

←Older revision		Revision as of 07:30, 10 June 2020
Line 1:		Line 1:

	==Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 70786556)==		==Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 70786556)==
-	<StructureSection load='5j5a' size='340' side='right' caption='[[5j5a]], [[Resolution\|resolution]] 2.70Å' scene=''>	+	<StructureSection load='5j5a' size='340' side='right'caption='[[5j5a]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j5a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5A OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5J5A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j5a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Tryb2 Tryb2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J5A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=756:[(3S)-3-(1H-BENZIMIDAZOL-2-YL)PIPERIDIN-1-YL](2-METHYL-1-BENZOFURAN-5-YL)METHANONE'>756</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=756:[(3S)-3-(1H-BENZIMIDAZOL-2-YL)PIPERIDIN-1-YL](2-METHYL-1-BENZOFURAN-5-YL)METHANONE'>756</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb10.70.6470 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=185431 TRYB2])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </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=5j5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5a OCA], [http://pdbe.org/5j5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5a RCSB], [http://www.ebi.ac.uk/pdbsum/5j5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5a ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5j5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5a OCA], [http://pdbe.org/5j5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5a RCSB], [http://www.ebi.ac.uk/pdbsum/5j5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5a ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 21:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Methionine--tRNA ligase]]		[[Category: Methionine--tRNA ligase]]
		+	[[Category: Tryb2]]
	[[Category: Barros-Alvarez, X]]		[[Category: Barros-Alvarez, X]]
	[[Category: Hol, W G.J]]		[[Category: Hol, W G.J]]

OCA at 23:26, 25 January 2017

OCA — Wed, 25 Jan 2017 23:26:07 GMT

←Older revision		Revision as of 23:26, 25 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5j5a is ~~ON HOLD until Paper~~ Publication	+	==Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 70786556)==
		+	<StructureSection load='5j5a' size='340' side='right' caption='[[5j5a]], [[Resolution\|resolution]] 2.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5j5a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J5A FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=756:[(3S)-3-(1H-BENZIMIDAZOL-2-YL)PIPERIDIN-1-YL](2-METHYL-1-BENZOFURAN-5-YL)METHANONE'>756</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </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=5j5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5a OCA], [http://pdbe.org/5j5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5a RCSB], [http://www.ebi.ac.uk/pdbsum/5j5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5a ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A screening hit 1 against Trypanosoma brucei methionyl-tRNA synthetase was optimized using a structure-guided approach. The optimization led to the identification of two novel series of potent inhibitors, the cyclic linker and linear linker series. Compounds of both series were potent in a T. brucei growth inhibition assay while showing low toxicity to mammalian cells. The best compound of each series, 16 and 31, exhibited EC50s of 39 and 22 nM, respectively. Compounds 16 and 31 also exhibited promising PK properties after oral dosing in mice. Moreover, compound 31 had moderately good brain permeability, with a brain/plasma ratio of 0.27 at 60 min after IP injection. This study provides new lead compounds for arriving at new treatments of human African trypanosomiasis (HAT).

-	~~Authors:~~ Barros-Alvarez, X., Koh, ~~C.Y.~~, Hol, W.G.J.	+	Structure-guided design of novel Trypanosoma brucei Methionyl-tRNA synthetase inhibitors.,Huang W, Zhang Z, Barros-Alvarez X, Koh CY, Ranade RM, Gillespie JR, Creason SA, Shibata S, Verlinde CL, Hol WG, Buckner FS, Fan E Eur J Med Chem. 2016 Nov 29;124:1081-1092. doi: 10.1016/j.ejmech.2016.10.024., Epub 2016 Oct 14. PMID:27788467<ref>PMID:27788467</ref>

-	~~Description: Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 70786556)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Hol, W.G.J~~]]	+	<div class="pdbe-citations 5j5a" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Methionine--tRNA ligase]]
	[[Category: Barros-Alvarez, X]]		[[Category: Barros-Alvarez, X]]
-	[[Category: Koh, C.Y]]	+	[[Category: Hol, W G.J]]
		+	[[Category: Koh, C Y]]
		+	[[Category: Inhibitor]]
		+	[[Category: Ligase]]
		+	[[Category: Ligase-ligase inhibitor complex]]
		+	[[Category: Methionine]]
		+	[[Category: Synthetase]]

OCA at 13:06, 9 September 2016

OCA — Fri, 09 Sep 2016 13:06:31 GMT

←Older revision		Revision as of 13:06, 9 September 2016
Line 5:		Line 5:
	Authors: Barros-Alvarez, X., Koh, C.Y., Hol, W.G.J.		Authors: Barros-Alvarez, X., Koh, C.Y., Hol, W.G.J.

-	Description: Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor ~~2-[1-(2-methyl-1-benzofuran-5-carbonyl)piperidin-3-yl]-1H-1,3-benzodiazole~~ (Chem 70786556)	+	Description: Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor (Chem 70786556)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Hol, W.G.J]]		[[Category: Hol, W.G.J]]
	[[Category: Barros-Alvarez, X]]		[[Category: Barros-Alvarez, X]]
	[[Category: Koh, C.Y]]		[[Category: Koh, C.Y]]

OCA at 15:04, 15 May 2016

OCA — Sun, 15 May 2016 15:04:08 GMT

←Older revision		Revision as of 15:04, 15 May 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5j5a is ON HOLD	+	The entry 5j5a is ON HOLD until Paper Publication

	Authors: Barros-Alvarez, X., Koh, C.Y., Hol, W.G.J.		Authors: Barros-Alvarez, X., Koh, C.Y., Hol, W.G.J.

OCA: Protected "5j5a" [edit=sysop:move=sysop]

OCA — Wed, 11 May 2016 01:28:55 GMT

Protected "5j5a" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:28, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5j5a is ON HOLD Authors: Barros-Alvarez, X., Koh, C.Y., Hol, W.G.J. Description: Trypanosoma brucei methionyl-tRNA synthetase in complex with inhib...

OCA — Wed, 11 May 2016 01:28:54 GMT

New page: '''Unreleased structure''' The entry 5j5a is ON HOLD Authors: Barros-Alvarez, X., Koh, C.Y., Hol, W.G.J. Description: Trypanosoma brucei methionyl-tRNA synthetase in complex with inhib...

New page

'''Unreleased structure'''

The entry 5j5a is ON HOLD

Authors: Barros-Alvarez, X., Koh, C.Y., Hol, W.G.J.

Description: Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor 2-[1-(2-methyl-1-benzofuran-5-carbonyl)piperidin-3-yl]-1H-1,3-benzodiazole (Chem 70786556)
[[Category: Unreleased Structures]]
[[Category: Hol, W.G.J]]
[[Category: Barros-Alvarez, X]]
[[Category: Koh, C.Y]]