View source for 6c04


==Mtb RNAP Holo/RbpA/double fork DNA -closed clamp==
<SX load='6c04' size='340' side='right' viewer='molstar' caption='[[6c04]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6c04]] is a 11 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C04 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C04 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rpoA, rpoA_1, CLD25_18970 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), rpoB, SAMEA2682864_01701 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), rpoC, rpoC_1, CLD25_03785 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), rpoZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), sigA, hrdB_2, CLD25_14885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), rbpA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6c04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c04 OCA], [http://pdbe.org/6c04 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c04 RCSB], [http://www.ebi.ac.uk/pdbsum/6c04 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c04 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/A0A045IP01_MYCTX A0A045IP01_MYCTX]] Binds to RNA polymerase (RNAP), stimulating transcription from principal, but not alternative sigma factor promoters.[HAMAP-Rule:MF_01483] [[http://www.uniprot.org/uniprot/A0A045J9E2_MYCTX A0A045J9E2_MYCTX]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU004279][SAAS:SAAS00365746] [[http://www.uniprot.org/uniprot/V9Z879_MYCTX V9Z879_MYCTX]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU363031] [[http://www.uniprot.org/uniprot/A0A045J8T1_MYCTX A0A045J8T1_MYCTX]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059] [[http://www.uniprot.org/uniprot/A0A0T9N9K3_MYCTX A0A0T9N9K3_MYCTX]] Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.[HAMAP-Rule:MF_00366][SAAS:SAAS00298387] [[http://www.uniprot.org/uniprot/A0A045HD00_MYCTX A0A045HD00_MYCTX]] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth.[SAAS:SAAS00535554] 
<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 6c04" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sigma factor 3D structures|Sigma factor 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: DNA-directed RNA polymerase]]
[[Category: Large Structures]]
[[Category: Campbell, E A]]
[[Category: Chen, J]]
[[Category: Darst, S A]]
[[Category: Lilic, M]]
[[Category: Selcuk, H Boyaci]]
[[Category: Closed clamp]]
[[Category: Initiation]]
[[Category: Transcription]]
[[Category: Transcription bubble]]
[[Category: Transcription-dna complex]]