6ykt: Difference between revisions

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 ==Neisseria gonorrhoeae Leucyl-tRNA Synthetase in Complex with Compound 11e==
-<StructureSection load='6ykt' size='340' side='right'caption='[[6ykt]]' scene=''>
+<StructureSection load='6ykt' size='340' side='right'caption='[[6ykt]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YKT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YKT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ykt]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"diplococcus_gonorrhoeae"_(zopf_1885)_lehmann_and_neumann_1896 "diplococcus gonorrhoeae" (zopf 1885) lehmann and neumann 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YKT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YKT 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=6ykt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ykt OCA], [http://pdbe.org/6ykt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ykt RCSB], [http://www.ebi.ac.uk/pdbsum/6ykt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ykt ProSAT]</span></td></tr>
+</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=OVN:[(2~{R},3~{S},4~{S},5~{R})-3,4-bis(oxidanyl)-5-[3-[4-(4-oxidanylbutyl)-1,2,3-triazol-1-yl]propyl]oxan-2-yl]methyl+~{N}-[(2~{S})-2-azanyl-4-methyl-pentanoyl]sulfamate'>OVN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6ykl|6ykl]], [[6ykn|6ykn]], [[6yko|6yko]], [[6ykq|6ykq]], [[6yks|6yks]]</div></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">leuS, VT05_02036, WHOO_00006, WHOO_00455 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=485 "Diplococcus gonorrhoeae" (Zopf 1885) Lehmann and Neumann 1896])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leucine--tRNA_ligase Leucine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.4 6.1.1.4] </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=6ykt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ykt OCA], [http://pdbe.org/6ykt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ykt RCSB], [http://www.ebi.ac.uk/pdbsum/6ykt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ykt ProSAT]</span></td></tr>
 </table>
+<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.
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6ykt" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Pang L]]
+[[Category: Leucine--tRNA ligase]]
-[[Category: Strelkov SV]]
+[[Category: Pang, L]]
-[[Category: Weeks SD]]
+[[Category: Strelkov, S V]]
+[[Category: Weeks, S D]]
+[[Category: Ligase]]
+[[Category: Protein-inhibitor complex]]
+[[Category: Rossmann fold]]
+[[Category: Trna synthetase]]