View source for 4p72


==PheRS in complex with compound 2a==
<StructureSection load='4p72' size='340' side='right'caption='[[4p72]], [[Resolution|resolution]] 2.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4p72]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P72 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]] 2.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2NL:2-{3-[(4-CHLOROPYRIDIN-2-YL)AMINO]PHENOXY}-N-METHYLACETAMIDE'>2NL</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=4p72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p72 OCA], [https://pdbe.org/4p72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p72 RCSB], [https://www.ebi.ac.uk/pdbsum/4p72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p72 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYFB_PSEAE SYFB_PSEAE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The antimicrobial activity of phenyl-thiazolylurea-sulfonamides against S. aureus PheRS are dependent upon phenylalanine levels in the extracellular fluids. Inhibitor efficacy in animal models of infection is substantially diminished by dietary phenylalanine intake, thereby reducing the perceived clinical utility of this inhibitor class. The search for novel antibacterial compounds against Gram-negative pathogens led to a re-evaluation of this phenomenon, which is shown here to be unique to S. aureus. Inhibition of macromolecular syntheses and characterization of novel resistance mutations in Escherichia coli demonstrate that antimicrobial activity of phenyl-thiazolylurea-sulfonamides is mediated by PheRS inhibition, validating this enzyme as a viable drug discovery target for Gram-negative pathogens. A search for novel inhibitors of PheRS yielded three novel chemical starting points. NMR studies were used to confirm direct target engagement for phenylalanine-competitive hits. The crystallographic structure of P. aeruginosa PheRS defined the binding modes of these hits, and revealed an auxiliary hydrophobic pocket that is positioned adjacent to the phenylalanine binding site. Three viable inhibitor-resistant mutants were mapped to this pocket, suggesting that this region is a potential liability for drug discovery.

The Role of a Novel Auxiliary Pocket in Bacterial Phenylalanyl-tRNA Synthetase Druggability.,Abibi A, Ferguson AD, Fleming PR, Gao N, Hajec LI, Hu J, Laganas VA, McKinney DC, McLeod SM, Prince DB, Shapiro AB, Buurman ET J Biol Chem. 2014 Jun 16. pii: jbc.M114.574061. PMID:24936059<ref>PMID:24936059</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4p72" 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: Pseudomonas aeruginosa PAO1]]
[[Category: Ferguson AD]]