View source for 3zju


==Ternary complex of E .coli leucyl-tRNA synthetase, tRNA(Leu) and the benzoxaborole AN3016 in the editing conformation==
<StructureSection load='3zju' size='340' side='right'caption='[[3zju]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zju]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZJU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZJU FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DJF:[(1S,5R,6R,8R)-6-(6-AMINOPURIN-9-YL)-2-(3-OXIDANYLPROPOXY)SPIRO[2,4,7-TRIOXA-3-BORANUIDABICYCLO[3.3.0]OCTANE-3,9-8-OXA-9-BORANUIDABICYCLO[4.3.0]NONA-1(6),2,4-TRIENE]-8-YL]METHYL+DIHYDROGEN+PHOSPHATE'>DJF</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;'>[[3zjt|3zjt]], [[3zjv|3zjv]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Leucine--tRNA_ligase Leucine--tRNA ligase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3zju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zju OCA], [https://pdbe.org/3zju PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zju RCSB], [https://www.ebi.ac.uk/pdbsum/3zju PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zju ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Gram-negative bacteria cause approximately 70% of the infections in intensive care units. A growing number of bacterial isolates responsible for these infections are resistant to currently available antibiotics and to many in development. Most agents under development are modifications of existing drug classes, which only partially overcome existing resistance mechanisms. Therefore, new classes of Gram-negative antibacterials with truly novel modes of action are needed to circumvent these existing resistance mechanisms. We have previously identified a new a way to inhibit an aminoacyl-tRNA synthetase, leucyl-tRNA synthetase (LeuRS), in fungi via the oxaborole tRNA trapping (OBORT) mechanism. Herein, we show how we have modified the OBORT mechanism using a structure-guided approach to develop a new boron-based antibiotic class, the aminomethylbenzoxaboroles, which inhibit bacterial leucyl-tRNA synthetase and have activity against Gram-negative bacteria by largely evading the main efflux mechanisms in Escherichia coli and Pseudomonas aeruginosa. The lead analogue, AN3365, is active against Gram-negative bacteria, including Enterobacteriaceae bearing NDM-1 and KPC carbapenemases, as well as P. aeruginosa. This novel boron-based antibacterial, AN3365, has good mouse pharmacokinetics and was efficacious against E. coli and P. aeruginosa in murine thigh infection models, which suggest that this novel class of antibacterials has the potential to address this unmet medical need.

Discovery of a novel class of boron-based antibacterials with activity against gram-negative bacteria.,Hernandez V, Crepin T, Palencia A, Cusack S, Akama T, Baker SJ, Bu W, Feng L, Freund YR, Liu L, Meewan M, Mohan M, Mao W, Rock FL, Sexton H, Sheoran A, Zhang Y, Zhang YK, Zhou Y, Nieman JA, Anugula MR, Keramane el M, Savariraj K, Reddy DS, Sharma R, Subedi R, Singh R, O'Leary A, Simon NL, De Marsh PL, Mushtaq S, Warner M, Livermore DM, Alley MR, Plattner JJ Antimicrob Agents Chemother. 2013 Mar;57(3):1394-403. doi: 10.1128/AAC.02058-12. , Epub 2013 Jan 7. PMID:23295920<ref>PMID:23295920</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zju" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
*[[Transfer RNA (tRNA)|Transfer RNA (tRNA)]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus coli migula 1895]]
[[Category: Large Structures]]
[[Category: Leucine--tRNA ligase]]
[[Category: Akama, T]]
[[Category: Alley, M R.K]]
[[Category: Anugula, M R]]
[[Category: Baker, S J]]
[[Category: Bu, W]]
[[Category: Crepin, T]]
[[Category: Cusack, S]]
[[Category: DeMarsh, P L]]
[[Category: Feng, L]]
[[Category: Freund, Y R]]
[[Category: Hernandez, V]]
[[Category: Keramane, E M]]
[[Category: Liu, L]]
[[Category: Livermore, D M]]
[[Category: Mao, W]]
[[Category: Meewan, M]]
[[Category: Mohan, M]]
[[Category: Mushtaq, S]]
[[Category: Nieman, J A]]
[[Category: OLeary, A]]
[[Category: Palencia, A]]
[[Category: Plattner, J J]]
[[Category: Reddy, D S]]
[[Category: Rock, F L]]
[[Category: Savariraj, K]]
[[Category: Sexton, H]]
[[Category: Sharma, R]]
[[Category: Sheoran, A]]
[[Category: Simon, N L]]
[[Category: Singh, R]]
[[Category: Subedi, R]]
[[Category: Warner, M]]
[[Category: Zhang, Y]]
[[Category: Zhou, Y]]
[[Category: Aminoacyl trna synthetase]]
[[Category: Atp binding]]
[[Category: Class i aminoacyl-trna synthetase]]
[[Category: Editing synthetase]]
[[Category: Ligase-rna complex]]
[[Category: Protein biosynthesis]]