2a68

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[[Image:2a68.gif|left|200px]]
 
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==Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic rifabutin==
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The line below this paragraph, containing "STRUCTURE_2a68", creates the "Structure Box" on the page.
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<StructureSection load='2a68' size='340' side='right'caption='[[2a68]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2a68]] 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=2A68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A68 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<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=RBT:RIFABUTIN'>RBT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_2a68| PDB=2a68 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2a68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a68 OCA], [https://pdbe.org/2a68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a68 RCSB], [https://www.ebi.ac.uk/pdbsum/2a68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a68 ProSAT], [https://www.topsan.org/Proteins/RSGI/2a68 TOPSAN]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a6/2a68_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2a68 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic rifabutin'''
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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>
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==Overview==
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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.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2A68 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A68 OCA].
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</div>
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<div class="pdbe-citations 2a68" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/16096056 16096056]
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*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
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[[Category: DNA-directed RNA polymerase]]
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*[[Sigma factor 3D structures|Sigma factor 3D structures]]
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[[Category: Protein complex]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Thermus thermophilus]]
[[Category: Thermus thermophilus]]
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[[Category: Artsimovitch, I.]]
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[[Category: Artsimovitch I]]
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[[Category: Igarashi, N.]]
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[[Category: Igarashi N]]
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[[Category: Matsugaki, N.]]
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[[Category: Matsugaki N]]
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[[Category: Perederina, A.]]
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[[Category: Perederina A]]
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[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
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[[Category: Svetlov D]]
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[[Category: Svetlov, D.]]
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[[Category: Svetlov V]]
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[[Category: Svetlov, V.]]
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[[Category: Tahirov TH]]
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[[Category: Tahirov, T H.]]
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[[Category: Vassylyev DG]]
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[[Category: Vassylyev, D G.]]
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[[Category: Vassylyeva MN]]
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[[Category: Vassylyeva, M N.]]
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[[Category: Wakatsuki S]]
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[[Category: Wakatsuki, S.]]
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[[Category: Antibiotic]]
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[[Category: Rifabutin]]
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[[Category: Riken structural genomics/proteomics initiative]]
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[[Category: Rna polymerase holoenzyme]]
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[[Category: Rsgi]]
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[[Category: Structural genomic]]
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[[Category: Transcription regulation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:39:35 2008''
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Current revision

Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic rifabutin

PDB ID 2a68

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