6ykl: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Unreleased structure'''
-The entry 6ykl is ON HOLD  until Paper Publication
+==Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound 11k==
+<StructureSection load='6ykl' size='340' side='right'caption='[[6ykl]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ykl]] 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=6YKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YKL FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27&#8491;</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=OVH:[(2~{R},3~{S},4~{S},5~{R})-3,4-bis(oxidanyl)-5-[3-(4-phenyl-1,2,3-triazol-1-yl)propyl]oxan-2-yl]methyl+~{N}-[(2~{S})-2-azanyl-4-methyl-pentanoyl]sulfamate'>OVH</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=6ykl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ykl OCA], [https://pdbe.org/6ykl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ykl RCSB], [https://www.ebi.ac.uk/pdbsum/6ykl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ykl ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SYL_NEIG1 SYL_NEIG1]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Leucyl-tRNA synthetase (LeuRS) is a clinically validated target for the development of antimicrobials. This enzyme catalyzes the formation of charged tRNA(Leu) molecules, an essential substrate for protein translation. In the first step of catalysis LeuRS activates leucine using ATP, forming a leucyl-adenylate intermediate. Bi-substrate inhibitors that mimic this chemically labile phosphoanhydride-linked nucleoside have proven to be potent inhibitors of different members of the aminoacyl-tRNA synthetase family but, to date, they have demonstrated poor antibacterial activity. We synthesized a small series of 1,5-anhydrohexitol-based analogues coupled to a variety of triazoles and performed detailed structure-activity relationship studies with bacterial LeuRS. In an in vitro assay, Ki(app) values in the nanomolar range were demonstrated. Inhibitory activity differences between the compounds revealed that the polarity and size of the triazole substituents affect binding. X-ray crystallographic studies of N. gonorrhoeae LeuRS in complex with all the inhibitors highlighted the crucial interactions defining their relative enzyme inhibitory activities. We further examined their in vitro antimicrobial properties by screening against several bacterial and yeast strains. While only weak antibacterial activity against M. tuberculosis was detected, the extensive structural data which were obtained could make these LeuRS inhibitors a suitable starting point towards further antibiotic development.
-Authors: Pang, L., Strelkov, S.V., Weeks, S.D.
+Synthesis and structure-activity studies of novel anhydrohexitol-based Leucyl-tRNA synthetase inhibitors.,De Ruysscher D, Pang L, Lenders SMG, Cappoen D, Cos P, Rozenski J, Strelkov SV, Weeks SD, Van Aerschot A Eur J Med Chem. 2020 Nov 16:113021. doi: 10.1016/j.ejmech.2020.113021. PMID:33248851<ref>PMID:33248851</ref>
-Description: Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound 11k
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Pang, L]]
+<div class="pdbe-citations 6ykl" style="background-color:#fffaf0;"></div>
-[[Category: Strelkov, S.V]]
-[[Category: Weeks, S.D]]
+==See Also==
+*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Neisseria gonorrhoeae]]
+[[Category: Pang L]]
+[[Category: Strelkov SV]]
+[[Category: Weeks SD]]