1xpr: Difference between revisions

New page: left|200px<br /><applet load="1xpr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xpr, resolution 3.15Å" /> '''Structural mechanism...
 
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'''Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic 5a-formylbicyclomycin (FB)'''<br />


==Overview==
==Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic 5a-formylbicyclomycin (FB)==
Rho is a hexameric RNA/DNA helicase/translocase that terminates, transcription of select genes in bacteria. The naturally occurring, antibiotic, bicyclomycin (BCM), acts as a noncompetitive inhibitor of ATP, turnover to disrupt this process. We have determined three independent, X-ray crystal structures of Rho complexed with BCM and two semisynthetic, derivatives, 5a-(3-formylphenylsulfanyl)-dihydrobicyclomycin (FPDB) and, 5a-formylbicyclomycin (FB) to 3.15, 3.05, and 3.15 A resolution, respectively. The structures show that BCM and its derivatives are, nonnucleotide inhibitors that interact with Rho at a pocket adjacent to, the ATP and RNA binding sites in the C-terminal half of the protein. BCM, association prevents ATP turnover by an unexpected mechanism, occluding, the binding of the nucleophilic water molecule required for ATP, hydrolysis. Our data explain why only certain elements of BCM have been, amenable to modification and serve as a template for the design of new, inhibitors.
<StructureSection load='1xpr' size='340' side='right'caption='[[1xpr]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xpr]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XPR 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]] 3.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=FB:5A-FORMYLBICYCLOMYCIN'>FB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1xpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xpr OCA], [https://pdbe.org/1xpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xpr RCSB], [https://www.ebi.ac.uk/pdbsum/1xpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xpr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RHO_ECOLI RHO_ECOLI] Facilitates transcription termination by a mechanism that involves rho binding to the nascent RNA, activation of rho's RNA-dependent ATPase activity, and release of the mRNA from the DNA template. RNA-dependent NTPAse which utilizes all four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01884]
== 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/xp/1xpr_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=1xpr ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1XPR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MG, AGS and FB as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XPR OCA].
*[[Helicase 3D structures|Helicase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin., Skordalakes E, Brogan AP, Park BS, Kohn H, Berger JM, Structure. 2005 Jan;13(1):99-109. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15642265 15642265]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Berger, J.M.]]
[[Category: Berger JM]]
[[Category: Brogan, A.P.]]
[[Category: Brogan AP]]
[[Category: Kohn, H.]]
[[Category: Kohn H]]
[[Category: Park, B.S.]]
[[Category: Park BS]]
[[Category: Skordalakes, E.]]
[[Category: Skordalakes E]]
[[Category: AGS]]
[[Category: FB]]
[[Category: MG]]
[[Category: rho; 5a-formylbicyclomycin; fb; atpgammas]]
 
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