View source for 5uag


==Escherichia coli RNA polymerase mutant - RpoB D516V==
<StructureSection load='5uag' size='340' side='right'caption='[[5uag]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5uag]] 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=5UAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UAG 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]] 3.399&#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=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=5uag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uag OCA], [https://pdbe.org/5uag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uag RCSB], [https://www.ebi.ac.uk/pdbsum/5uag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uag 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]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Since 1967, Rifampin (RMP, a Rifamycin) has been used as a first line antibiotic treatment for tuberculosis (TB), and it remains the cornerstone of current short-term TB treatment. Increased occurrence of Rifamycin-resistant (RIFR ) TB, approximately 41% of which results from the RpoB S531L mutation in RNA polymerase (RNAP), has become a growing problem worldwide. In this study, we determined the X-ray crystal structures of the Escherichia coli RNAPs containing the most clinically important S531L mutation and two other frequently observed RIFR mutants, RpoB D516V and RpoB H526Y. The structures reveal that the S531L mutation imparts subtle if any structural or functional impact on RNAP in the absence of RIF. However, upon RMP binding, the S531L mutant exhibits a disordering of the RIF binding interface, which effectively reduces the RMP affinity. In contrast, the H526Y mutation reshapes the RIF binding pocket, generating significant steric conflicts that essentially prevent any RIF binding. While the D516V mutant does not exhibit any such gross structural changes, certainly the electrostatic surface of the RIF binding pocket is dramatically changed, likely resulting in the decreased affinity for RIFs. Analysis of interactions of RMP with three common RIFR mutant RNAPs suggests that modifications to RMP may recover its efficacy against RIFR TB.

Structural basis for rifamycin resistance of bacterial RNA polymerase by the three most clinically important RpoB mutations found in Mycobacterium tuberculosis.,Molodtsov V, Scharf NT, Stefan MA, Garcia GA, Murakami KS Mol Microbiol. 2016 Dec 23. doi: 10.1111/mmi.13606. PMID:28009073<ref>PMID:28009073</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5uag" 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: Garcia GA]]
[[Category: Molodtsov V]]
[[Category: Murakami KS]]
[[Category: Scharf NT]]
[[Category: Stefan MA]]