5uh8: Difference between revisions

<StructureSection load='5uh8' size='340' side='right'caption='[[5uh8]], [[Resolution|resolution]] 4.18&Aring;' scene=''>

<table><tr><td colspan='2'>[[5uh8]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UH8 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]] 4.176&#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=5uh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uh8 OCA], [https://pdbe.org/5uh8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uh8 RCSB], [https://www.ebi.ac.uk/pdbsum/5uh8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uh8 ProSAT]</span></td></tr>

[https://www.uniprot.org/uniprot/RPOA_MYCTU RPOA_MYCTU] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059]<ref>PMID:22570422</ref>  

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Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug rifampin (Rif). We report crystal structures of Mtb RNAP, alone and in complex with Rif, at 3.8-4.4 A resolution. The results identify an Mtb-specific structural module of Mtb RNAP and establish that Rif functions by a steric-occlusion mechanism that prevents extension of RNA. We also report non-Rif-related compounds-Nalpha-aroyl-N-aryl-phenylalaninamides (AAPs)-that potently and selectively inhibit Mtb RNAP and Mtb growth, and we report crystal structures of Mtb RNAP in complex with AAPs. AAPs bind to a different site on Mtb RNAP than Rif, exhibit no cross-resistance with Rif, function additively when co-administered with Rif, and suppress resistance emergence when co-administered with Rif.

 

Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition.,Lin W, Mandal S, Degen D, Liu Y, Ebright YW, Li S, Feng Y, Zhang Y, Mandal S, Jiang Y, Liu S, Gigliotti M, Talaue M, Connell N, Das K, Arnold E, Ebright RH Mol Cell. 2017 Apr 20;66(2):169-179.e8. doi: 10.1016/j.molcel.2017.03.001. Epub, 2017 Apr 6. PMID:28392175<ref>PMID:28392175</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 5uh8" style="background-color:#fffaf0;"></div>

 

[[Category: Large Structures]]

[[Category: Mycobacterium tuberculosis H37Rv]]

[[Category: Das K]]

[[Category: Ebright RH]]

[[Category: Feng Y]]

[[Category: Lin W]]