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| | ==Structure of a uracil-DNA glycosylase (ung) from Coxiella burnetii== | | ==Structure of a uracil-DNA glycosylase (ung) from Coxiella burnetii== |
| - | <StructureSection load='3tr7' size='340' side='right' caption='[[3tr7]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='3tr7' size='340' side='right'caption='[[3tr7]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tr7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"rickettsia_burneti"_(sic)_derrick_1939 "rickettsia burneti" (sic) derrick 1939]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TR7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tr7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxiella_burnetii Coxiella burnetii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TR7 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1958Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBU_0988, ung ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=777 "Rickettsia burneti" (sic) Derrick 1939])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uracil-DNA_glycosylase Uracil-DNA glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.27 3.2.2.27] </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=3tr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tr7 OCA], [https://pdbe.org/3tr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tr7 RCSB], [https://www.ebi.ac.uk/pdbsum/3tr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tr7 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=3tr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tr7 OCA], [http://pdbe.org/3tr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tr7 RCSB], [http://www.ebi.ac.uk/pdbsum/3tr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tr7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UNG_COXBU UNG_COXBU]] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.[HAMAP-Rule:MF_00148] | + | [https://www.uniprot.org/uniprot/UNG_COXBU UNG_COXBU] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.[HAMAP-Rule:MF_00148] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3tr7" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3tr7" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Uracil-DNA glycosylase]] | + | [[Category: Coxiella burnetii]] |
| - | [[Category: Burshteyn, F]] | + | [[Category: Large Structures]] |
| - | [[Category: Cassidy, M]] | + | [[Category: Burshteyn F]] |
| - | [[Category: Cheung, J]] | + | [[Category: Cassidy M]] |
| - | [[Category: Franklin, M C]] | + | [[Category: Cheung J]] |
| - | [[Category: Gary, E]] | + | [[Category: Franklin MC]] |
| - | [[Category: Love, J]] | + | [[Category: Gary E]] |
| - | [[Category: Rudolph, M]] | + | [[Category: Love J]] |
| - | [[Category: Dna metabolism]]
| + | [[Category: Rudolph M]] |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
UNG_COXBU Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.[HAMAP-Rule:MF_00148]
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.
See Also
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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