View source for 5ags


==Crystal structure of the LeuRS editing domain of Mycobacterium tuberculosis in complex with the adduct 3-(Aminomethyl)-4-bromo-7-ethoxybenzo[c][1,2]oxaborol-1(3H)-ol-AMP==
<StructureSection load='5ags' size='340' side='right'caption='[[5ags]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ags]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AGS 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]] 1.47&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38Y:3-(AMINOMETHYL)-4-BROMO-7-ETHOXYBENZO[C][1,2]OXABOROL-1(3H)-OL-MODIFIED+ADENOSINE'>38Y</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</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=5ags FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ags OCA], [https://pdbe.org/5ags PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ags RCSB], [https://www.ebi.ac.uk/pdbsum/5ags PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ags ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYL_MYCTU SYL_MYCTU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The recent development and spread of extensively (XDR) and totally resistant (TDR) strains of Mycobacterium tuberculosis, highlights the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although the parenteral aminoglycosides are a key component in multidrug-resistant (MDR) TB therapy, the oxazolidinone, linezolid, is the only orally available protein synthesis inhibitor that is effective against TB. Herein, we show that small molecule inhibitors of aminoacyl-tRNA synthetases (AARS), known to be excellent antibacterial protein synthesis targets, can be designed that are orally bioavailable and effective against M. tuberculosis in TB mouse infection models. We applied the oxaborole tRNA trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), to M. tuberculosis LeuRS. X-ray crystallography was used to guide design of LeuRS inhibitors that have good biochemical potency and excellent whole cell activity against M. tuberculosis Importantly, their good oral bioavailability translates into in vivo efficacy in both the acute and chronic mouse models of TB with comparable potency to the frontline drug isoniazid.

Discovery of novel oral protein synthesis inhibitors of Mycobacterium tuberculosis that target leucyl-tRNA synthetase.,Palencia A, Li X, Bu W, Choi W, Ding CZ, Easom EE, Feng L, Hernandez V, Houston P, Liu L, Meewan M, Mohan M, Rock FL, Sexton H, Zhang S, Zhou Y, Wan B, Wang Y, Franzblau SG, Woolhiser L, Gruppo V, Lenaerts AJ, O'Malley T, Parish T, Cooper CB, Waters MG, Ma Z, Ioerger TR, Sacchettini JC, Rullas J, Angulo-Barturen I, Perez-Herran E, Mendoza A, Barros D, Cusack S, Plattner JJ, Alley MR Antimicrob Agents Chemother. 2016 Aug 8. pii: AAC.01339-16. PMID:27503647<ref>PMID:27503647</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ags" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Alley MRK]]
[[Category: Barros D]]
[[Category: Cooper CB]]
[[Category: Cusack S]]
[[Category: Ding C]]
[[Category: Easom EE]]
[[Category: Franzblau SG]]
[[Category: Hernandez V]]
[[Category: Lenaerts AJ]]
[[Category: Li X]]
[[Category: Ma Z]]
[[Category: Meewan M]]
[[Category: Mendoza A]]
[[Category: Mohan M]]
[[Category: Palencia A]]
[[Category: Parish T]]
[[Category: Plattner JJ]]
[[Category: Rock FL]]
[[Category: Wang Y]]
[[Category: Waters MG]]