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| ==CRYSTAL STRUCTURE of UROPORPHYRINOGEN DECARBOXYLASE (UPD) FROM BURKHOLDERIA THAILANDENSIS E264== | | ==CRYSTAL STRUCTURE of UROPORPHYRINOGEN DECARBOXYLASE (UPD) FROM BURKHOLDERIA THAILANDENSIS E264== |
| <StructureSection load='4exq' size='340' side='right' caption='[[4exq]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='4exq' size='340' side='right'caption='[[4exq]], [[Resolution|resolution]] 1.65Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4exq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Burkholderia_thailandensis_e264 Burkholderia thailandensis e264]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EXQ FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4exq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_thailandensis_E264 Burkholderia thailandensis E264]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EXQ FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ex4|4ex4]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hemE, BTH_I3304 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=271848 Burkholderia thailandensis E264])</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=4exq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4exq OCA], [https://pdbe.org/4exq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4exq RCSB], [https://www.ebi.ac.uk/pdbsum/4exq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4exq ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uroporphyrinogen_decarboxylase Uroporphyrinogen decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.37 4.1.1.37] </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=4exq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4exq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4exq RCSB], [http://www.ebi.ac.uk/pdbsum/4exq PDBsum]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/DCUP_BURTA DCUP_BURTA] Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III (By similarity). |
| 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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| 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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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Burkholderia thailandensis e264]] | | [[Category: Burkholderia thailandensis E264]] |
| [[Category: Uroporphyrinogen decarboxylase]] | | [[Category: Large Structures]] |
| [[Category: Structural genomic]]
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| [[Category: Biosynthetic protein]]
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| [[Category: Heme biosynthesis]]
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| [[Category: National institute of allergy and infectious disease]]
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| [[Category: Niaid]]
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| [[Category: Nih]]
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| [[Category: Sbri]]
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| [[Category: Ssgcid]]
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| [[Category: Uro-d]]
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