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New page: left|200px<br /><applet load="2a69" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a69, resolution 2.50Å" /> '''Crystal structure of... |
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== | ==Crystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with antibiotic rifapentin== | ||
Rifamycins, the clinically important antibiotics, target bacterial RNA | <StructureSection load='2a69' size='340' side='right'caption='[[2a69]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2a69]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A69 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RPT:RIFAPENTINE'>RPT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2a69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a69 OCA], [https://pdbe.org/2a69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a69 RCSB], [https://www.ebi.ac.uk/pdbsum/2a69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a69 ProSAT], [https://www.topsan.org/Proteins/RSGI/2a69 TOPSAN]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RPOA_THET8 RPOA_THET8] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a6/2a69_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a69 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Rifamycins, the clinically important antibiotics, target bacterial RNA polymerase (RNAP). A proposed mechanism in which rifamycins sterically block the extension of nascent RNA beyond three nucleotides does not alone explain why certain RNAP mutations confer resistance to some but not other rifamycins. Here we show that unlike rifampicin and rifapentin, and contradictory to the steric model, rifabutin inhibits formation of the first and second phosphodiester bonds. We report 2.5 A resolution structures of rifabutin and rifapentin complexed with the Thermus thermophilus RNAP holoenzyme. The structures reveal functionally important distinct interactions of antibiotics with the initiation sigma factor. Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo-holoenzyme, whereas an increase in Mg2+ concentration confers resistance to rifamycins. We propose that a rifamycin-induced signal is transmitted over approximately 19 A to the RNAP active site to slow down catalysis. Based on structural predictions, we designed enzyme substitutions that apparently interrupt this allosteric signal. | |||
Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins.,Artsimovitch I, Vassylyeva MN, Svetlov D, Svetlov V, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Tahirov TH, Vassylyev DG Cell. 2005 Aug 12;122(3):351-63. PMID:16096056<ref>PMID:16096056</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 2a69" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | |||
*[[Sigma factor 3D structures|Sigma factor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
[[Category: Artsimovitch | [[Category: Artsimovitch I]] | ||
[[Category: Igarashi | [[Category: Igarashi N]] | ||
[[Category: Matsugaki | [[Category: Matsugaki N]] | ||
[[Category: Perederina | [[Category: Perederina A]] | ||
[[Category: Svetlov D]] | |||
[[Category: Svetlov | [[Category: Svetlov V]] | ||
[[Category: Svetlov | [[Category: Tahirov TH]] | ||
[[Category: Tahirov | [[Category: Vassylyev DG]] | ||
[[Category: Vassylyev | [[Category: Vassylyeva MN]] | ||
[[Category: Vassylyeva | [[Category: Wakatsuki S]] | ||
[[Category: Wakatsuki | |||
Latest revision as of 10:19, 23 August 2023
Crystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with antibiotic rifapentinCrystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with antibiotic rifapentin
Structural highlights
FunctionRPOA_THET8 DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRifamycins, the clinically important antibiotics, target bacterial RNA polymerase (RNAP). A proposed mechanism in which rifamycins sterically block the extension of nascent RNA beyond three nucleotides does not alone explain why certain RNAP mutations confer resistance to some but not other rifamycins. Here we show that unlike rifampicin and rifapentin, and contradictory to the steric model, rifabutin inhibits formation of the first and second phosphodiester bonds. We report 2.5 A resolution structures of rifabutin and rifapentin complexed with the Thermus thermophilus RNAP holoenzyme. The structures reveal functionally important distinct interactions of antibiotics with the initiation sigma factor. Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo-holoenzyme, whereas an increase in Mg2+ concentration confers resistance to rifamycins. We propose that a rifamycin-induced signal is transmitted over approximately 19 A to the RNAP active site to slow down catalysis. Based on structural predictions, we designed enzyme substitutions that apparently interrupt this allosteric signal. Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins.,Artsimovitch I, Vassylyeva MN, Svetlov D, Svetlov V, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Tahirov TH, Vassylyev DG Cell. 2005 Aug 12;122(3):351-63. PMID:16096056[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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