4k47

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==Structure of the Streptococcus pneumoniae leucyl-tRNA synthetase editing domain bound to a benzoxaborole-AMP adduct==
==Structure of the Streptococcus pneumoniae leucyl-tRNA synthetase editing domain bound to a benzoxaborole-AMP adduct==
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<StructureSection load='4k47' size='340' side='right' caption='[[4k47]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
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<StructureSection load='4k47' size='340' side='right'caption='[[4k47]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4k47]] is a 1 chain structure with sequence from [http://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=4K47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K47 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4k47]] 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=4K47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K47 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WMP:[(1R,5R,6R,8S)-6-(6-AMINOPURIN-9-YL)-3-[(R)-OXIDANYL(PHENYL)METHYL]SPIRO[2,4,7-TRIOXA-3-BORANUIDABICYCLO[3.3.0]OCTANE-3,9-8-OXA-9-BORANUIDABICYCLO[4.3.0]NONA-1,3,5-TRIENE]-8-YL]METHYL+DIHYDROGEN+PHOSPHATE'>WMP</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k48|4k48]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WMP:[(1R,5R,6R,8S)-6-(6-AMINOPURIN-9-YL)-3-[(R)-OXIDANYL(PHENYL)METHYL]SPIRO[2,4,7-TRIOXA-3-BORANUIDABICYCLO[3.3.0]OCTANE-3,9-8-OXA-9-BORANUIDABICYCLO[4.3.0]NONA-1,3,5-TRIENE]-8-YL]METHYL+DIHYDROGEN+PHOSPHATE'>WMP</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">leuS, SPN23F02440 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=561276 Streptococcus pneumoniae ATCC 700669])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4k47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k47 OCA], [https://pdbe.org/4k47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k47 RCSB], [https://www.ebi.ac.uk/pdbsum/4k47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k47 ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leucine--tRNA_ligase Leucine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.4 6.1.1.4] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k47 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k47 RCSB], [http://www.ebi.ac.uk/pdbsum/4k47 PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/SYL_STRPJ SYL_STRPJ]
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Streptococcus pneumoniae causes bacterial pneumonia with high mortality and morbidity. The emergency of multidrug-resistant bacteria threatens the treatment of the disease. Leucyl-tRNA synthetase (LeuRS) plays an essential role in cellular translation and is an attractive drug target for antimicrobial development. Here we report the compound ZCL039, a benzoxaborole-based derivative of AN2690, as a potent anti-pneumococcal agent that inhibits S. pneumoniae LeuRS (SpLeuRS) activity. We show using kinetic, biochemical analyses combined with the crystal structure of ZCL039-AMP in complex with the separated SpLeuRS editing domain, that ZCL039 binds to the LeuRS editing active site which requires the presence of tRNA(Leu), and employs an uncompetitive inhibition mechanism. Further docking models establish that ZCL039 clashes with the eukaryal/archaeal specific insertion I4ae helix within editing domains. These findings demonstrate the potential of benzoxaboroles as effective LeuRS inhibitors for pneumococcus infection therapy, and provide future structure-guided drug design and optimization.
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Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase.,Hu QH, Liu RJ, Fang ZP, Zhang J, Ding YY, Tan M, Wang M, Pan W, Zhou HC, Wang ED Sci Rep. 2013 Aug 20;3:2475. doi: 10.1038/srep02475. PMID:23959225<ref>PMID:23959225</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Leucine--tRNA ligase]]
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[[Category: Large Structures]]
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[[Category: Streptococcus pneumoniae atcc 700669]]
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[[Category: Streptococcus pneumoniae ATCC 700669]]
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[[Category: Ding, Y Y]]
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[[Category: Ding YY]]
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[[Category: Fang, Z P]]
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[[Category: Fang ZP]]
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[[Category: Hu, Q H]]
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[[Category: Hu QH]]
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[[Category: Liu, R J]]
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[[Category: Liu RJ]]
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[[Category: Pan, W]]
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[[Category: Pan W]]
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[[Category: Tan, M]]
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[[Category: Tan M]]
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[[Category: Wang, E D]]
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[[Category: Wang ED]]
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[[Category: Wang, M]]
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[[Category: Wang M]]
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[[Category: Zhang, J]]
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[[Category: Zhang J]]
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[[Category: Zhou, H C]]
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[[Category: Zhou HC]]
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[[Category: Antibacterial]]
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[[Category: Benzoxaborole]]
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[[Category: Leucyl-trna synthetase]]
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[[Category: Ligase-ligase inhibitor complex]]
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Current revision

Structure of the Streptococcus pneumoniae leucyl-tRNA synthetase editing domain bound to a benzoxaborole-AMP adduct

PDB ID 4k47

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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