View source for 6c06


==Mycobacterium tuberculosis RNAP Holo/RbpA/Fidaxomicin==
<SX load='6c06' size='340' side='right' viewer='molstar' caption='[[6c06]], [[Resolution|resolution]] 5.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6c06]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C06 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FI8:[(2~{R},3~{S},4~{S},5~{S},6~{R})-6-[[(3~{E},5~{E},8~{S},9~{E},11~{S},12~{R},13~{E},15~{E},18~{S})-12-[(2~{R},3~{S},4~{R},5~{S})-6,6-dimethyl-5-(2-methylpropanoyloxy)-3,4-bis(oxidanyl)oxan-2-yl]oxy-11-ethyl-9,13,15-trimethyl-8-oxidanyl-18-[(1~{R})-1-oxidanylethyl]-2-oxidanylidene-1-oxacyclooctadeca-3,5,9,13,15-pentaen-3-yl]methoxy]-5-methoxy-2-methyl-4-oxidanyl-oxan-3-yl]+3,5-bis(chloranyl)-2-ethyl-4,6-bis(oxidanyl)benzoate'>FI8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6c06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c06 OCA], [https://pdbe.org/6c06 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c06 RCSB], [https://www.ebi.ac.uk/pdbsum/6c06 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c06 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPOA_MYCTU RPOA_MYCTU] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059]<ref>PMID:22570422</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective against Mycobacterium tuberculosis RNAP in vitro, but clinical use of Fdx is limited to treating Clostridium difficile intestinal infections due to poor absorption. To identify the structural determinants of Fdx binding to RNAP, we determined the 3.4 A cryo-electron microscopy structure of a complete M. tuberculosis RNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin, explaining its strong effect on M. tuberculosis. Additional structures define conformational states of M. tuberculosis RNAP between the free apo-holoenzyme and the promoter-engaged open complex ready for transcription. The results establish that Fdx acts like a doorstop to jam the enzyme in an open state, preventing the motions necessary to secure promoter DNA in the active site. Our results provide a structural platform to guide development of anti-tuberculosis antimicrobials based on the Fdx binding pocket.

Fidaxomicin jams Mycobacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts.,Boyaci H, Chen J, Lilic M, Palka M, Mooney RA, Landick R, Darst SA, Campbell EA Elife. 2018 Feb 26;7. pii: 34823. doi: 10.7554/eLife.34823. PMID:29480804<ref>PMID:29480804</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6c06" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sigma factor 3D structures|Sigma factor 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Boyaci Selcuk H]]
[[Category: Campbell EA]]
[[Category: Chen J]]
[[Category: Darst SA]]
[[Category: Lilic M]]