View source for 3zjt


==Ternary complex of E.coli leucyl-tRNA synthetase, tRNA(Leu)574 and the benzoxaborole AN3017 in the editing conformation==
<StructureSection load='3zjt' size='340' side='right'caption='[[3zjt]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zjt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZJT 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=574:[(3AS,4R,6R,6AR)-2-{2-[(1S)-2-AMINO-1-HYDROXYETHYL]PHENYL}-6-(6-AMINO-9H-PURIN-9-YL)TETRAHYDROFURO[3,4-D][1,3,2]DIOXABOROL-4-YL]METHYL+DIHYDROGEN+PHOSPHITE'>574</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=3zjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zjt OCA], [https://pdbe.org/3zjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zjt RCSB], [https://www.ebi.ac.uk/pdbsum/3zjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zjt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYL_ECOLI SYL_ECOLI] 
<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 3zjt" 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: Escherichia coli]]
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Akama T]]
[[Category: Alley MRK]]
[[Category: Anugula MR]]
[[Category: Baker SJ]]
[[Category: Bu W]]
[[Category: Crepin T]]
[[Category: Cusack S]]
[[Category: DeMarsh PL]]
[[Category: Feng L]]
[[Category: Freund YR]]
[[Category: Hernandez V]]
[[Category: Keramane EM]]
[[Category: Liu L]]
[[Category: Livermore DM]]
[[Category: Mao W]]
[[Category: Meewan M]]
[[Category: Mohan M]]
[[Category: Mushtaq S]]
[[Category: Nieman JA]]
[[Category: OLeary A]]
[[Category: Palencia A]]
[[Category: Plattner JJ]]
[[Category: Reddy DS]]
[[Category: Rock FL]]
[[Category: Savariraj K]]
[[Category: Sexton H]]
[[Category: Sharma R]]
[[Category: Sheoran A]]
[[Category: Simon NL]]
[[Category: Singh R]]
[[Category: Subedi R]]
[[Category: Warner M]]
[[Category: Zhang Y]]
[[Category: Zhou Y]]