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| | ==Structure of an acylphosphatase from Coxiella burnetii== | | ==Structure of an acylphosphatase from Coxiella burnetii== |
| - | <StructureSection load='3trg' size='340' side='right' caption='[[3trg]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='3trg' size='340' side='right'caption='[[3trg]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3trg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Coxbu Coxbu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TRG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3trg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxiella_burnetii_RSA_493 Coxiella burnetii RSA 493]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TRG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.601Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acyP, CBU_1995 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227377 COXBU])</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=3trg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3trg OCA], [https://pdbe.org/3trg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3trg RCSB], [https://www.ebi.ac.uk/pdbsum/3trg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3trg 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/Acylphosphatase Acylphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.7 3.6.1.7] </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=3trg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3trg OCA], [http://pdbe.org/3trg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3trg RCSB], [http://www.ebi.ac.uk/pdbsum/3trg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3trg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ACYP_COXBU ACYP_COXBU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acylphosphatase]] | + | [[Category: Coxiella burnetii RSA 493]] |
| - | [[Category: Coxbu]] | + | [[Category: Large Structures]] |
| - | [[Category: Burshteyn, F]] | + | [[Category: Burshteyn F]] |
| - | [[Category: Cassidy, M]] | + | [[Category: Cassidy M]] |
| - | [[Category: Cheung, J]] | + | [[Category: Cheung J]] |
| - | [[Category: Franklin, M C]] | + | [[Category: Franklin MC]] |
| - | [[Category: Gary, E]] | + | [[Category: Gary E]] |
| - | [[Category: Love, J]] | + | [[Category: Love J]] |
| - | [[Category: Rudolph, M]] | + | [[Category: Rudolph M]] |
| - | [[Category: Fatty acid and phospholipid metabolism]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
ACYP_COXBU
Publication Abstract from PubMed
Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C. burnetii that have great potential as drug targets. We used high-throughput techniques to produce novel crystal structures of 48 of these proteins. We selected one protein, C. burnetii dihydrofolate reductase (CbDHFR), for additional work to demonstrate the value of these structures for structure-based drug design. This enzyme's structure reveals a feature in the substrate binding groove that is different between CbDHFR and human dihydrofolate reductase (hDFHR). We then identified a compound by in silico screening that exploits this binding groove difference, and demonstrated that this compound inhibits CbDHFR with at least 25-fold greater potency than hDHFR. Since this binding groove feature is shared by many other prokaryotes, the compound identified could form the basis of a novel antibacterial agent effective against a broad spectrum of pathogenic bacteria. This article is protected by copyright. All rights reserved.
Structural Genomics for Drug Design against the Pathogen Coxiella burnetii.,Franklin MC, Cheung J, Rudolph MJ, Burshteyn F, Cassidy M, Gary E, Hillerich B, Yao ZK, Carlier PR, Totrov M, Love JD Proteins. 2015 Jun 1. doi: 10.1002/prot.24841. PMID:26033498[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Franklin MC, Cheung J, Rudolph MJ, Burshteyn F, Cassidy M, Gary E, Hillerich B, Yao ZK, Carlier PR, Totrov M, Love JD. Structural Genomics for Drug Design against the Pathogen Coxiella burnetii. Proteins. 2015 Jun 1. doi: 10.1002/prot.24841. PMID:26033498 doi:http://dx.doi.org/10.1002/prot.24841
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