OCA at 12:13, 1 February 2024

2024-02-01T12:13:19Z

←Older revision		Revision as of 12:13, 1 February 2024
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	==Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound LeuS7HMDDA==		==Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound LeuS7HMDDA==
-	<StructureSection load='7ap2' size='340' side='right'caption='[[7ap2]]' scene=''>	+	<StructureSection load='7ap2' size='340' side='right'caption='[[7ap2]], [[Resolution\|resolution]] 2.25Å' 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=7AP2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7AP2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ap2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae Neisseria gonorrhoeae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AP2 FirstGlance]. <br>
-	</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=7ap2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ap2 OCA], [~~http~~://pdbe.org/7ap2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7ap2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7ap2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7ap2 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]] 2.25Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RRW:[(2~{R},3~{S},4~{R},5~{R})-5-[7-azanyl-5-(hydroxymethyl)benzimidazol-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+~{N}-[(2~{S})-2-azanyl-4-methyl-pentanoyl]sulfamate'>RRW</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7ap2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ap2 OCA], [https://pdbe.org/7ap2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ap2 RCSB], [https://www.ebi.ac.uk/pdbsum/7ap2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ap2 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SYL_NEIG1 SYL_NEIG1]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aminoacyl-tRNA synthetases (aaRSs) have become viable targets for the development of antimicrobial agents due to their crucial role in protein translation. A series of six amino acids were coupled to the purine-like 7-amino-5-hydroxymethylbenzimidazole nucleoside analogue following an optimized synthetic pathway. These compounds were designed as aaRS inhibitors and can be considered as 1,3-dideazaadenine analogues carrying a 2-hydroxymethyl substituent. Despite our intentions to obtain N(1)-glycosylated 4-aminobenzimidazole congeners, resembling the natural purine nucleosides glycosylated at the N(9)-position, we obtained the N(3)-glycosylated benzimidazole derivatives as the major products, resembling the respective purine N(7)-glycosylated nucleosides. A series of X-ray crystal structures of class I and II aaRSs in complex with newly synthesized compounds revealed interesting interactions of these "base-flipped" analogues with their targets. While the exocyclic amine of the flipped base mimics the reciprocal interaction of the N(3)-purine atom of aminoacyl-sulfamoyl adenosine (aaSA) congeners, the hydroxymethyl substituent of the flipped base apparently loses part of the standard interactions of the adenine N(1) and the N(6)-amine as seen with aaSA analogues. Upon the evaluation of the inhibitory potency of the newly obtained analogues, nanomolar inhibitory activities were noted for the leucine and isoleucine analogues targeting class I aaRS enzymes, while rather weak inhibitory activity against the corresponding class II aaRSs was observed. This class bias could be further explained by detailed structural analysis.
		+
		+	Synthesis and Biological Evaluation of 1,3-Dideazapurine-Like 7-Amino-5-Hydroxymethyl-Benzimidazole Ribonucleoside Analogues as Aminoacyl-tRNA Synthetase Inhibitors.,Zhang B, Pang L, Nautiyal M, De Graef S, Gadakh B, Lescrinier E, Rozenski J, Strelkov SV, Weeks SD, Van Aerschot A Molecules. 2020 Oct 16;25(20). pii: molecules25204751. doi:, 10.3390/molecules25204751. PMID:33081246<ref>PMID:33081246</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ap2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Neisseria gonorrhoeae]]
	[[Category: De Graef S]]		[[Category: De Graef S]]
	[[Category: Pang L]]		[[Category: Pang L]]
	[[Category: Strelkov SV]]		[[Category: Strelkov SV]]
	[[Category: Weeks SD]]		[[Category: Weeks SD]]

OCA at 20:37, 28 October 2020

2020-10-28T20:37:14Z

←Older revision		Revision as of 20:37, 28 October 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 7ap2 ~~is ON HOLD~~	+	==Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound LeuS7HMDDA==
-		+	<StructureSection load='7ap2' size='340' side='right'caption='[[7ap2]]' scene=''>
-	~~Authors~~: ~~Pang~~, L., ~~De Graef~~, S., ~~Strelkov, S~~.V., ~~Weeks, S~~.D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AP2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AP2 FirstGlance]. <br>
-	~~Description: Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound Leu-HMDDA~~	+	</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=7ap2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ap2 OCA], [http://pdbe.org/7ap2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ap2 RCSB], [http://www.ebi.ac.uk/pdbsum/7ap2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ap2 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Weeks,~~ S.D]]	+	__TOC__
-	[[Category: ~~De Graef, S~~]]	+	</StructureSection>
-	[[Category: Strelkov~~, S.V~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Pang, L~~]]	+	[[Category: De Graef S]]
		+	[[Category: Pang L]]
		+	[[Category: Strelkov SV]]
		+	[[Category: Weeks SD]]

OCA: Protected "7ap2" [edit=sysop:move=sysop]

2020-10-21T06:40:41Z

Protected "7ap2" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:40, 21 October 2020

OCA: New page: '''Unreleased structure''' The entry 7ap2 is ON HOLD Authors: Pang, L., De Graef, S., Strelkov, S.V., Weeks, S.D. Description: Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex w...

2020-10-21T06:40:39Z

New page: '''Unreleased structure''' The entry 7ap2 is ON HOLD Authors: Pang, L., De Graef, S., Strelkov, S.V., Weeks, S.D. Description: Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex w...

New page

'''Unreleased structure'''

The entry 7ap2 is ON HOLD

Authors: Pang, L., De Graef, S., Strelkov, S.V., Weeks, S.D.

Description: Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound Leu-HMDDA
[[Category: Unreleased Structures]]
[[Category: Weeks, S.D]]
[[Category: De Graef, S]]
[[Category: Strelkov, S.V]]
[[Category: Pang, L]]

7ap2 - Revision history

OCA at 12:13, 1 February 2024

OCA at 20:37, 28 October 2020

OCA: Protected "7ap2" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7ap2 is ON HOLD Authors: Pang, L., De Graef, S., Strelkov, S.V., Weeks, S.D. Description: Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex w...