View source for 6ccv


==Crystal structure of a Mycobacterium smegmatis RNA polymerase transcription initiation complex with inhibitor Rifampicin==
<StructureSection load='6ccv' size='340' side='right'caption='[[6ccv]], [[Resolution|resolution]] 3.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ccv]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CCV 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]] 3.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=RFP:RIFAMPICIN'>RFP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6ccv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ccv OCA], [https://pdbe.org/6ccv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ccv RCSB], [https://www.ebi.ac.uk/pdbsum/6ccv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ccv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPOA_MYCS2 RPOA_MYCS2] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059]<ref>PMID:19926651</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rifamycin antibiotics (Rifs) target bacterial RNA polymerases (RNAPs) and are widely used to treat infections including tuberculosis. The utility of these compounds is threatened by the increasing incidence of resistance (Rif(R)). As resistance mechanisms found in clinical settings may also occur in natural environments, here we postulated that bacteria could have evolved to produce rifamycin congeners active against clinically relevant resistance phenotypes. We survey soil metagenomes and identify a tailoring enzyme-rich family of gene clusters encoding biosynthesis of rifamycin congeners (kanglemycins, Kangs) with potent in vivo and in vitro activity against the most common clinically relevant Rif(R) mutations. Our structural and mechanistic analyses reveal the basis for Kang inhibition of Rif(R) RNAP. Unlike Rifs, Kangs function through a mechanism that includes interfering with 5'-initiating substrate binding. Our results suggest that examining soil microbiomes for new analogues of clinically used antibiotics may uncover metabolites capable of circumventing clinically important resistance mechanisms.

Rifamycin congeners kanglemycins are active against rifampicin-resistant bacteria via a distinct mechanism.,Peek J, Lilic M, Montiel D, Milshteyn A, Woodworth I, Biggins JB, Ternei MA, Calle PY, Danziger M, Warrier T, Saito K, Braffman N, Fay A, Glickman MS, Darst SA, Campbell EA, Brady SF Nat Commun. 2018 Oct 8;9(1):4147. doi: 10.1038/s41467-018-06587-2. PMID:30297823<ref>PMID:30297823</ref>

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

==See Also==
*[[Sigma factor 3D structures|Sigma factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Synthetic construct]]
[[Category: Campbell EA]]
[[Category: Darst SA]]
[[Category: Lilic M]]