View source for 6vjs


==Escherichia coli RNA polymerase and ureidothiophene-2-carboxylic acid complex==
<StructureSection load='6vjs' size='340' side='right'caption='[[6vjs]], [[Resolution|resolution]] 4.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vjs]] 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=6VJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VJS 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]] 4.02&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QZY:3-{[benzyl(ethyl)carbamoyl]amino}-5-(4-phenoxyphenyl)thiophene-2-carboxylic+acid'>QZY</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=6vjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vjs OCA], [https://pdbe.org/6vjs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vjs RCSB], [https://www.ebi.ac.uk/pdbsum/6vjs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vjs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPOA_ECOLI RPOA_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. This subunit plays an important role in subunit assembly since its dimerization is the first step in the sequential assembly of subunits to form the holoenzyme.[HAMAP-Rule:MF_00059]
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== Publication Abstract from PubMed ==
Chronic wounds infected with pathogens such as Staphylococcus aureus represent a worldwide health concern, especially in patients with a compromised immune system. As antimicrobial resistance has become an immense global problem, novel antibiotics are urgently needed. One strategy to overcome this threatening situation is the search for drugs targeting novel binding sites on essential and validated enzymes such as the bacterial RNA polymerase (RNAP). In this work, we describe the establishment of an in vivo wound infection model based on the pathogen S. aureus and hairless Crl:SKH1-Hrhr (SKH1) mice. The model proved to be a valuable preclinical tool to study selected RNAP inhibitors after topical application. While rifampicin showed a reduction in the loss of body weight induced by the bacteria, an acceleration of wound healing kinetics, and a reduced number of colony forming units in the wound, the ureidothiophene-2-carboxylic acid 1 was inactive under in vivo conditions, probably due to strong plasma protein binding. The cocrystal structure of compound 1 with RNAP, that we hereby also present, will be of great value for applying appropriate structural modifications to further optimize the compound, especially in terms of plasma protein binding.

Evaluation of Bacterial RNA Polymerase Inhibitors in a Staphylococcus aureus-Based Wound Infection Model in SKH1 Mice.,Haupenthal J, Kautz Y, Elgaher WAM, Patzold L, Rohrig T, Laschke MW, Tschernig T, Hirsch AKH, Molodtsov V, Murakami KS, Hartmann RW, Bischoff M ACS Infect Dis. 2020 Sep 21. doi: 10.1021/acsinfecdis.0c00034. PMID:32886885<ref>PMID:32886885</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6vjs" 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/>
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Molodtsov V]]
[[Category: Murakami KS]]