View source for 7bzj


==The Discovery of Benzhydrol-Oxaborole Hybrid Derivatives as Leucyl-tRNA Synthetase Inhibitors==
<StructureSection load='7bzj' size='340' side='right'caption='[[7bzj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7bzj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_ATCC_700669 Streptococcus pneumoniae ATCC 700669]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BZJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BZJ 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FGX:[(1~{R},5~{R},6~{S},8~{R})-8-(6-aminopurin-9-yl)-4-[(~{R})-oxidanyl-[4-(2-oxidanylidenepropylsulfanyl)phenyl]methyl]spiro[2,4,7-trioxa-3-boranuidabicyclo[3.3.0]octane-3,7-7-boranuidabicyclo[4.3.0]nona-1(6),2,4-triene]-6-yl]methoxy-tris(oxidanyl)phosphanium'>FGX</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=7bzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bzj OCA], [https://pdbe.org/7bzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bzj RCSB], [https://www.ebi.ac.uk/pdbsum/7bzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bzj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYL_STRPJ SYL_STRPJ] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pneumonia caused by bacterium S. pneumoniae is a severe acute respiratory infectious disease with high morbidity and mortality, especially for children and immunity-compromised patients. The emergence of multidrug-resistant S. pneumoniae also presents a challenge to human health. Leucyl-tRNA synthetase (LeuRS) catalyzes the attachment of l-leucine to tRNA(Leu), which plays an essential role in protein translation and is considered an attractive antimicrobial drug target. In the present work, benzhydrol-oxaborole hybrid compounds were designed and synthesized as inhibitors of S. pneumoniae LeuRS. Exploration of the phenyl ring near Lysine 389 eventually yielded compounds 46 and 54 with submicromolar inhibitory potency. The co-crystal of compound 54 in the editing domain pocket of SpLeuRS was obtained and confirmed the formation of an additional hydrogen bond between the carbonyl of 54 and Lysine 389. It also showed anti-pneumococcal activity in vitro. The structure-activity relationship was discussed. This work will provide an essential foundation for the further development of anti-pneumococcal agents by targeting LeuRS.

Discovery of benzhydrol-oxaborole derivatives as Streptococcus pneumoniae leucyl-tRNA synthetase inhibitors.,Hao G, Li H, Yang F, Dong D, Li Z, Ding Y, Pan W, Wang E, Liu R, Zhou H Bioorg Med Chem. 2020 Nov 13:115871. doi: 10.1016/j.bmc.2020.115871. PMID:33221064<ref>PMID:33221064</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7bzj" 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: Streptococcus pneumoniae ATCC 700669]]
[[Category: Li H]]
[[Category: Liu RJ]]
[[Category: Wang ED]]
[[Category: Zhou H]]