7qi8 - Revision history

OCA at 07:57, 7 February 2024

2024-02-07T07:57:42Z

←Older revision		Revision as of 07:57, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7qi8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QI8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7qi8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QI8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DD0:2-azanyl-6-[(1~{S},7~{S})-2,2-bis(fluoranyl)-7-oxidanyl-cycloheptyl]-4-methoxy-7~{H}-pyrrolo[3,4-d]pyrimidin-5-one'>DD0</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DD0:2-azanyl-6-[(1~{S},7~{S})-2,2-bis(fluoranyl)-7-oxidanyl-cycloheptyl]-4-methoxy-7~{H}-pyrrolo[3,4-d]pyrimidin-5-one'>DD0</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</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=7qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qi8 OCA], [https://pdbe.org/7qi8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qi8 RCSB], [https://www.ebi.ac.uk/pdbsum/7qi8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qi8 ProSAT]</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=7qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qi8 OCA], [https://pdbe.org/7qi8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qi8 RCSB], [https://www.ebi.ac.uk/pdbsum/7qi8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qi8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/SYK1_MYCTO SYK1_MYCTO]		[https://www.uniprot.org/uniprot/SYK1_MYCTO SYK1_MYCTO]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold.
-
-	Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs.,Green SR, Davis SH, Damerow S, Engelhart CA, Mathieson M, Baragana B, Robinson DA, Tamjar J, Dawson A, Tamaki FK, Buchanan KI, Post J, Dowers K, Shepherd SM, Jansen C, Zuccotto F, Gilbert IH, Epemolu O, Riley J, Stojanovski L, Osuna-Cabello M, Perez-Herran E, Rebollo MJ, Guijarro Lopez L, Casado Castro P, Camino I, Kim HC, Bean JM, Nahiyaan N, Rhee KY, Wang Q, Tan VY, Boshoff HIM, Converse PJ, Li SY, Chang YS, Fotouhi N, Upton AM, Nuermberger EL, Schnappinger D, Read KD, Encinas L, Bates RH, Wyatt PG, Cleghorn LAT Nat Commun. 2022 Oct 11;13(1):5992. doi: 10.1038/s41467-022-33736-5. PMID:36220877<ref>PMID:36220877</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7qi8" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 19:18, 19 October 2022

2022-10-19T19:18:51Z

←Older revision		Revision as of 19:18, 19 October 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7qi8 is ~~ON HOLD until Paper~~ Publication	+	==CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM Mycobacterium tuberculosis COMPLEXED WITH L-LYSINE AND INHIBITOR==
		+	<StructureSection load='7qi8' size='340' side='right'caption='[[7qi8]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7qi8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QI8 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DD0:2-azanyl-6-[(1~{S},7~{S})-2,2-bis(fluoranyl)-7-oxidanyl-cycloheptyl]-4-methoxy-7~{H}-pyrrolo[3,4-d]pyrimidin-5-one'>DD0</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</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=7qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qi8 OCA], [https://pdbe.org/7qi8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qi8 RCSB], [https://www.ebi.ac.uk/pdbsum/7qi8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qi8 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SYK1_MYCTO SYK1_MYCTO]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold.

-	~~Authors: Dawson~~, A., Robinson, D.A., ~~Tamjar~~, J., ~~Wyatt~~, P., ~~Green~~, S.	+	Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs.,Green SR, Davis SH, Damerow S, Engelhart CA, Mathieson M, Baragana B, Robinson DA, Tamjar J, Dawson A, Tamaki FK, Buchanan KI, Post J, Dowers K, Shepherd SM, Jansen C, Zuccotto F, Gilbert IH, Epemolu O, Riley J, Stojanovski L, Osuna-Cabello M, Perez-Herran E, Rebollo MJ, Guijarro Lopez L, Casado Castro P, Camino I, Kim HC, Bean JM, Nahiyaan N, Rhee KY, Wang Q, Tan VY, Boshoff HIM, Converse PJ, Li SY, Chang YS, Fotouhi N, Upton AM, Nuermberger EL, Schnappinger D, Read KD, Encinas L, Bates RH, Wyatt PG, Cleghorn LAT Nat Commun. 2022 Oct 11;13(1):5992. doi: 10.1038/s41467-022-33736-5. PMID:36220877<ref>PMID:36220877</ref>

-	~~Description: CRYSTAL STRUCTURE OF LYSYL~~-~~TRNA SYNTHETASE FROM Mycobacterium tuberculosis COMPLEXED WITH L~~-~~LYSINE AND INHIBITOR~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Green, S~~]]	+	<div class="pdbe-citations 7qi8" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Tamjar, J~~]]	+	== References ==
-	[[Category: Robinson~~, D.A~~]]	+	<references/>
-	[[Category: ~~Dawson, A~~]]	+	__TOC__
-	[[Category: Wyatt, P]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Mycobacterium tuberculosis]]
		+	[[Category: Dawson A]]
		+	[[Category: Green S]]
		+	[[Category: Robinson DA]]
		+	[[Category: Tamjar J]]
		+	[[Category: Wyatt P]]

OCA at 05:24, 2 February 2022

2022-02-02T05:24:05Z

←Older revision		Revision as of 05:24, 2 February 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7qi8 is ON HOLD	+	The entry 7qi8 is ON HOLD until Paper Publication

	Authors: Dawson, A., Robinson, D.A., Tamjar, J., Wyatt, P., Green, S.		Authors: Dawson, A., Robinson, D.A., Tamjar, J., Wyatt, P., Green, S.

-	Description: CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM Mycobacterium tuberculosis COMPLEXED WITH L-LYSINE	+	Description: CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM Mycobacterium tuberculosis COMPLEXED WITH L-LYSINE AND INHIBITOR
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Green, S]]		[[Category: Green, S]]
	[[Category: Tamjar, J]]		[[Category: Tamjar, J]]
-	[[Category: Wyatt, P]]
	[[Category: Robinson, D.A]]		[[Category: Robinson, D.A]]
	[[Category: Dawson, A]]		[[Category: Dawson, A]]
		+	[[Category: Wyatt, P]]

OCA: Protected "7qi8" [edit=sysop:move=sysop]

2021-12-22T13:56:46Z

Protected "7qi8" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:56, 22 December 2021

OCA: New page: '''Unreleased structure''' The entry 7qi8 is ON HOLD Authors: Dawson, A., Robinson, D.A., Tamjar, J., Wyatt, P., Green, S. Description: CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM ...

2021-12-22T13:56:44Z

New page: '''Unreleased structure''' The entry 7qi8 is ON HOLD Authors: Dawson, A., Robinson, D.A., Tamjar, J., Wyatt, P., Green, S. Description: CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM ...

New page

'''Unreleased structure'''

The entry 7qi8 is ON HOLD

Authors: Dawson, A., Robinson, D.A., Tamjar, J., Wyatt, P., Green, S.

Description: CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM Mycobacterium tuberculosis COMPLEXED WITH L-LYSINE
[[Category: Unreleased Structures]]
[[Category: Green, S]]
[[Category: Tamjar, J]]
[[Category: Wyatt, P]]
[[Category: Robinson, D.A]]
[[Category: Dawson, A]]