View source for 6wqt


==Xanthomonas citri Methionyl-tRNA synthetase in complex with REP3123==
<StructureSection load='6wqt' size='340' side='right'caption='[[6wqt]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wqt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xanthomonas_citri_pv._citri_str._306 Xanthomonas citri pv. citri str. 306]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WQT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WQT 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U81:5-[(3-{[(4R)-6,8-dibromo-3,4-dihydro-2H-1-benzopyran-4-yl]amino}propyl)amino]thieno[3,2-b]pyridin-7(6H)-one'>U81</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=6wqt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wqt OCA], [https://pdbe.org/6wqt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wqt RCSB], [https://www.ebi.ac.uk/pdbsum/6wqt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wqt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYM_XANAC SYM_XANAC] Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Gram-negative bacteria are responsible for a variety of human, animal and plant diseases. The spread of multidrug-resistant Gram-negative bacteria poses a challenge to disease control and highlights the need for novel antimicrobials. Due to their critical role in protein synthesis, aminoacyl-tRNA synthetases (AaRS), including the methionyl-tRNA synthetases MetRS1 and MetRS2, are attractive drug targets. MetRS1 has long been exploited as a drug target in Gram-positive bacteria and protozoan parasites. However, MetRS1 inhibitors have limited action upon Gram-negative pathogens or on Gram-positive bacteria that produce MetRS2 enzymes. The underlying mechanism by which MetRS2 enzymes are insensitive to MetRS1 inhibitors is presently unknown. Herein, we report the first structures of MetRS2 from a multidrug-resistant Gram-negative bacterium in its ligand-free state and bound to its substrate or MetRS1 inhibitors. The structures reveal the binding mode of two diaryldiamine MetRS1 inhibitors that occupy the amino acid-binding site and a surrounding auxiliary pocket implicated in tRNA acceptor arm binding. The structural features associated with amino acid polymorphisms found in the methionine and auxiliary pockets reveal the molecular basis for diaryldiamine binding and selectivity between MetRS1 and MetRS2 enzymes. Moreover, we show that mutations in key polymorphic residues in the methionine and auxiliary pockets not only altered inhibitor binding affinity, but also significantly reduced enzyme function. Our findings thus reinforce the tRNA acceptor arm binding site as a druggable pocket in class-I AaRS and provide a structural basis for optimization of MetRS2 inhibitors for the development of new antimicrobials against Gram-negative pathogens.

Molecular basis for diaryldiamine selectivity and competition with tRNA in a type-2 methionyl-tRNA synthetase from a Gram-negative bacterium.,Mercaldi GF, de Oliveira Andrade M, de Lima Zanella J, Cordeiro AT, Benedetti CE J Biol Chem. 2021 Apr 12:100658. doi: 10.1016/j.jbc.2021.100658. PMID:33857480<ref>PMID:33857480</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wqt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Xanthomonas citri pv. citri str. 306]]
[[Category: Benedetti CE]]
[[Category: Mercaldi GF]]