3tr8: Difference between revisions
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==Structure of an oligoribonuclease (orn) from Coxiella burnetii== | |||
<StructureSection load='3tr8' size='340' side='right'caption='[[3tr8]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3tr8]] is a 2 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=3TR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TR8 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.503Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=3tr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tr8 OCA], [https://pdbe.org/3tr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tr8 RCSB], [https://www.ebi.ac.uk/pdbsum/3tr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tr8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ORN_COXBU ORN_COXBU] 3'-to-5' exoribonuclease specific for small oligoribonucleotides.[HAMAP-Rule:MF_00045] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:26033498</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3tr8" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Ribonuclease|Ribonuclease]] | *[[Exonuclease 3D structures|Exonuclease 3D structures]] | ||
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Coxiella burnetii]] | [[Category: Coxiella burnetii]] | ||
[[Category: Burshteyn | [[Category: Large Structures]] | ||
[[Category: Cassidy | [[Category: Burshteyn F]] | ||
[[Category: Cheung | [[Category: Cassidy M]] | ||
[[Category: Franklin | [[Category: Cheung J]] | ||
[[Category: Gary | [[Category: Franklin MC]] | ||
[[Category: Love | [[Category: Gary E]] | ||
[[Category: Rudolph | [[Category: Love J]] | ||
[[Category: Rudolph M]] | |||
Latest revision as of 11:10, 9 October 2024
Structure of an oligoribonuclease (orn) from Coxiella burnetiiStructure of an oligoribonuclease (orn) from Coxiella burnetii
Structural highlights
FunctionORN_COXBU 3'-to-5' exoribonuclease specific for small oligoribonucleotides.[HAMAP-Rule:MF_00045] Publication Abstract from PubMedCoxiella 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 AlsoReferences
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