View source for 6cux


==Escherichia coli RpoB S531L mutant RNA polymerase holoenzyme in complex with Kanglemycin A==
<StructureSection load='6cux' size='340' side='right'caption='[[6cux]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cux]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CUX 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]] 4.104&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KNG:4-{(1S)-1-[(2S,12Z,16S,17R,18S,19R,20R,21S,22R,23S,24E)-21-(acetyloxy)-23-[(2,6-dideoxy-3,4-O-methylidene-beta-D-ribo-hexopyranosyl)oxy]-5,6,9,17,19-pentahydroxy-2,4,12,18,20,22-hexamethyl-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca[1,13]dienoimino)naphtho[2,1-b]furan-16-yl]ethoxy}-3,3-dimethyl-4-oxobutanoic+acid'>KNG</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=6cux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cux OCA], [https://pdbe.org/6cux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cux RCSB], [https://www.ebi.ac.uk/pdbsum/6cux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cux ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPOB_ECOLI RPOB_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibiotic-resistant bacterial pathogens pose an urgent healthcare threat, prompting a demand for new medicines. We report the mode of action of the natural ansamycin antibiotic kanglemycin A (KglA). KglA binds bacterial RNA polymerase at the rifampicin-binding pocket but maintains potency against RNA polymerases containing rifampicin-resistant mutations. KglA has antibiotic activity against rifampicin-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis (MDR-M. tuberculosis). The X-ray crystal structures of KglA with the Escherichia coli RNA polymerase holoenzyme and Thermus thermophilus RNA polymerase-promoter complex reveal an altered-compared with rifampicin-conformation of KglA within the rifampicin-binding pocket. Unique deoxysugar and succinate ansa bridge substituents make additional contacts with a separate, hydrophobic pocket of RNA polymerase and preclude the formation of initial dinucleotides, respectively. Previous ansa-chain modifications in the rifamycin series have proven unsuccessful. Thus, KglA represents a key starting point for the development of a new class of ansa-chain derivatized ansamycins to tackle rifampicin resistance.

Mode of Action of Kanglemycin A, an Ansamycin Natural Product that Is Active against Rifampicin-Resistant Mycobacterium tuberculosis.,Mosaei H, Molodtsov V, Kepplinger B, Harbottle J, Moon CW, Jeeves RE, Ceccaroni L, Shin Y, Morton-Laing S, Marrs ECL, Wills C, Clegg W, Yuzenkova Y, Perry JD, Bacon J, Errington J, Allenby NEE, Hall MJ, Murakami KS, Zenkin N Mol Cell. 2018 Sep 12. pii: S1097-2765(18)30688-9. doi:, 10.1016/j.molcel.2018.08.028. PMID:30244835<ref>PMID:30244835</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6cux" 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: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Molodtsov V]]
[[Category: Murakami KS]]