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| | <StructureSection load='3tqu' size='340' side='right'caption='[[3tqu]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='3tqu' size='340' side='right'caption='[[3tqu]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tqu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxbu Coxbu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TQU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tqu]] is a 4 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=3TQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TQU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 1.9Å</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=CA:CALCIUM+ION'>CA</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">CBU_0043 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227377 COXBU])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nucleoside-triphosphate_diphosphatase Nucleoside-triphosphate diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.19 3.6.1.19] </span></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=3tqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tqu OCA], [https://pdbe.org/3tqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tqu RCSB], [https://www.ebi.ac.uk/pdbsum/3tqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tqu ProSAT]</span></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=3tqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tqu OCA], [https://pdbe.org/3tqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tqu RCSB], [https://www.ebi.ac.uk/pdbsum/3tqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tqu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NTPA_COXBU NTPA_COXBU]] Pyrophosphatase that hydrolyzes non-canonical purine nucleotides such as XTP and ITP/dITP to their respective monophosphate derivatives. Might exclude non-canonical purines from DNA precursor pool, thus preventing their incorporation into DNA and avoiding chromosomal lesions (By similarity).
| + | [https://www.uniprot.org/uniprot/IXTPA_COXBU IXTPA_COXBU] Pyrophosphatase that catalyzes the hydrolysis of nucleoside triphosphates to their monophosphate derivatives, with a high preference for the non-canonical purine nucleotides XTP (xanthosine triphosphate), dITP (deoxyinosine triphosphate) and ITP. Seems to function as a house-cleaning enzyme that removes non-canonical purine nucleotides from the nucleotide pool, thus preventing their incorporation into DNA/RNA and avoiding chromosomal lesions.[HAMAP-Rule:MF_01405] |
| | <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: Coxbu]] | + | [[Category: Coxiella burnetii RSA 493]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nucleoside-triphosphate diphosphatase]]
| + | [[Category: Burshteyn F]] |
| - | [[Category: Burshteyn, F]] | + | [[Category: Cassidy M]] |
| - | [[Category: Cassidy, M]] | + | [[Category: Cheung J]] |
| - | [[Category: Cheung, J]] | + | [[Category: Franklin MC]] |
| - | [[Category: Franklin, M C]] | + | [[Category: Gary E]] |
| - | [[Category: Gary, E]] | + | [[Category: Love J]] |
| - | [[Category: Love, J]] | + | [[Category: Rudolph M]] |
| - | [[Category: Rudolph, M]] | + | |
| - | [[Category: Ham1 protein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
IXTPA_COXBU Pyrophosphatase that catalyzes the hydrolysis of nucleoside triphosphates to their monophosphate derivatives, with a high preference for the non-canonical purine nucleotides XTP (xanthosine triphosphate), dITP (deoxyinosine triphosphate) and ITP. Seems to function as a house-cleaning enzyme that removes non-canonical purine nucleotides from the nucleotide pool, thus preventing their incorporation into DNA/RNA and avoiding chromosomal lesions.[HAMAP-Rule:MF_01405]
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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