4ex5

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<StructureSection load='4ex5' size='340' side='right' caption='[[4ex5]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='4ex5' size='340' side='right' caption='[[4ex5]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4ex5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burta Burta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EX5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EX5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4ex5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EX5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EX5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BTH_I1883, lysS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=271848 BURTA])</td></tr>
 
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </span></td></tr>
<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=4ex5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ex5 OCA], [http://pdbe.org/4ex5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ex5 RCSB], [http://www.ebi.ac.uk/pdbsum/4ex5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ex5 ProSAT]</span></td></tr>
<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=4ex5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ex5 OCA], [http://pdbe.org/4ex5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ex5 RCSB], [http://www.ebi.ac.uk/pdbsum/4ex5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ex5 ProSAT]</span></td></tr>
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<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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BACKGROUND: The genus Burkholderia includes pathogenic gram-negative bacteria that cause melioidosis, glanders, and pulmonary infections of patients with cancer and cystic fibrosis. Drug resistance has made development of new antimicrobials critical. Many approaches to discovering new antimicrobials, such as structure-based drug design and whole cell phenotypic screens followed by lead refinement, require high-resolution structures of proteins essential to the parasite. METHODOLOGY/PRINCIPAL FINDINGS: We experimentally identified 406 putative essential genes in B. thailandensis, a low-virulence species phylogenetically similar to B. pseudomallei, the causative agent of melioidosis, using saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq). We selected 315 protein products of these genes based on structure-determination criteria, such as excluding very large and/or integral membrane proteins, and entered them into the Seattle Structural Genomics Center for Infection Disease (SSGCID) structure determination pipeline. To maximize structural coverage of these targets, we applied an "ortholog rescue" strategy for those producing insoluble or difficult to crystallize proteins, resulting in the addition of 387 orthologs (or paralogs) from seven other Burkholderia species into the SSGCID pipeline. This structural genomics approach yielded structures from 31 putative essential targets from B. thailandensis, and 25 orthologs from other Burkholderia species, yielding an overall structural coverage for 49 of the 406 essential gene families, with a total of 88 depositions into the Protein Data Bank. Of these, 25 proteins have properties of a potential antimicrobial drug target i.e., no close human homolog, part of an essential metabolic pathway, and a deep binding pocket. We describe the structures of several potential drug targets in detail. CONCLUSIONS/SIGNIFICANCE: This collection of structures, solubility and experimental essentiality data provides a resource for development of drugs against infections and diseases caused by Burkholderia. All expression clones and proteins created in this study are freely available by request.
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Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline. Here we investigate thirty-one aminoacyl-tRNA synthetases from infectious disease organisms by co-crystallization in the presence of their cognate amino acid, ATP, and/or inhibitors. Crystal structures were determined for a CysRS from Borrelia burgdorferi bound to AMP, GluRS from Borrelia burgdorferi and Burkholderia thailandensis bound to glutamic acid, a TrpRS from the eukaryotic pathogen Encephalitozoon cuniculi bound to tryptophan, a HisRS from Burkholderia thailandensis bound to histidine, and a LysRS from Burkholderia thailandensis bound to lysine. Thus, the presence of ligands may promote aaRS crystallization and structure determination. Comparison with homologous structures shows conformational flexibility that appears to be a recurring theme with this enzyme class.
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Combining functional and structural genomics to sample the essential Burkholderia structome.,Baugh L, Gallagher LA, Patrapuvich R, Clifton MC, Gardberg AS, Edwards TE, Armour B, Begley DW, Dieterich SH, Dranow DM, Abendroth J, Fairman JW, Fox D 3rd, Staker BL, Phan I, Gillespie A, Choi R, Nakazawa-Hewitt S, Nguyen MT, Napuli A, Barrett L, Buchko GW, Stacy R, Myler PJ, Stewart LJ, Manoil C, Van Voorhis WC PLoS One. 2013;8(1):e53851. doi: 10.1371/journal.pone.0053851. Epub 2013 Jan 31. PMID:23382856<ref>PMID:23382856</ref>
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Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms.,Moen SO, Edwards TE, Dranow DM, Clifton MC, Sankaran B, Van Voorhis WC, Sharma A, Manoil C, Staker BL, Myler PJ, Lorimer DD Sci Rep. 2017 Mar 16;7(1):223. doi: 10.1038/s41598-017-00367-6. PMID:28303005<ref>PMID:28303005</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Burta]]
 
[[Category: Lysine--tRNA ligase]]
[[Category: Lysine--tRNA ligase]]
[[Category: Structural genomic]]
[[Category: Structural genomic]]

Revision as of 07:20, 29 March 2017

Crystal structure of lysyl-tRNA synthetase LysRS from Burkholderia thailandensis bound to lysine

4ex5, resolution 2.40Å

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