View source for 7l7b


==Clostridioides difficile RNAP with fidaxomicin==
<StructureSection load='7l7b' size='340' side='right'caption='[[7l7b]], [[Resolution|resolution]] 3.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7l7b]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridia_bacterium Clostridia bacterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L7B 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]] 3.26&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FI8:Fidaxomicin'>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=7l7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7b OCA], [https://pdbe.org/7l7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7b RCSB], [https://www.ebi.ac.uk/pdbsum/7l7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7b ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPOA_CLOD6 RPOA_CLOD6] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fidaxomicin (Fdx) is widely used to treat Clostridioides difficile (Cdiff) infections, but the molecular basis of its narrow-spectrum activity in the human gut microbiome remains unknown. Cdiff infections are a leading cause of nosocomial deaths(1). Fidaxomicin, which inhibits RNA polymerase, targets Cdiff with minimal effects on gut commensals, reducing recurrence of Cdiff infection(2,3). Here we present the cryo-electron microscopy structure of Cdiff RNA polymerase in complex with fidaxomicin and identify a crucial fidaxomicin-binding determinant of Cdiff RNA polymerase that is absent in most gut microbiota such as Proteobacteria and Bacteroidetes. By combining structural, biochemical, genetic and bioinformatic analyses, we establish that a single residue in Cdiff RNA polymerase is a sensitizing element for fidaxomicin narrow-spectrum activity. Our results provide a blueprint for targeted drug design against an important human pathogen.

Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile.,Cao X, Boyaci H, Chen J, Bao Y, Landick R, Campbell EA Nature. 2022 Apr;604(7906):541-545. doi: 10.1038/s41586-022-04545-z. Epub 2022 , Apr 6. PMID:35388215<ref>PMID:35388215</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7l7b" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
*[[Sigma factor 3D structures|Sigma factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridia bacterium]]
[[Category: Large Structures]]
[[Category: Boyaci H]]
[[Category: Campbell EA]]
[[Category: Chen J]]
[[Category: Darst SA]]