5uh5

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Mycobacterium tuberculosis transcription initiation complex containing 3 nt of RNA

Structural highlights

5uh5 is a 9 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.746Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SIGA_MYCTU Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth (Probable).^[1] ^[2] ^[3]

Publication Abstract from PubMed

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Beaucher J, Rodrigue S, Jacques PE, Smith I, Brzezinski R, Gaudreau L. Novel Mycobacterium tuberculosis anti-sigma factor antagonists control sigmaF activity by distinct mechanisms. Mol Microbiol. 2002 Sep;45(6):1527-40. PMID:12354223
↑ Hartkoorn RC, Sala C, Magnet SJ, Chen JM, Pojer F, Cole ST. Sigma factor F does not prevent rifampin inhibition of RNA polymerase or cause rifampin tolerance in Mycobacterium tuberculosis. J Bacteriol. 2010 Oct;192(20):5472-9. doi: 10.1128/JB.00687-10. Epub 2010 Aug 20. PMID:20729364 doi:http://dx.doi.org/10.1128/JB.00687-10
↑ Hu Y, Morichaud Z, Chen S, Leonetti JP, Brodolin K. Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the sigma A-containing RNA polymerase holoenzyme. Nucleic Acids Res. 2012 Aug;40(14):6547-57. doi: 10.1093/nar/gks346. Epub 2012, May 8. PMID:22570422 doi:http://dx.doi.org/10.1093/nar/gks346
↑ 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. Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition. Mol Cell. 2017 Apr 20;66(2):169-179.e8. doi: 10.1016/j.molcel.2017.03.001. Epub, 2017 Apr 6. PMID:28392175 doi:http://dx.doi.org/10.1016/j.molcel.2017.03.001

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5uh5"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5uh5 is ON HOLD
+==Crystal structure of Mycobacterium tuberculosis transcription initiation complex containing 3 nt of RNA==
+<StructureSection load='5uh5' size='340' side='right'caption='[[5uh5]], [[Resolution|resolution]] 3.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5uh5]] 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=5UH5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UH5 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]] 3.746&#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=5uh5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uh5 OCA], [https://pdbe.org/5uh5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uh5 RCSB], [https://www.ebi.ac.uk/pdbsum/5uh5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uh5 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SIGA_MYCTU SIGA_MYCTU] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth (Probable).<ref>PMID:12354223</ref> <ref>PMID:20729364</ref> <ref>PMID:22570422</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5uh5" 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: Large Structures]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
+[[Category: Das K]]
+[[Category: Ebright RH]]
+[[Category: Feng Y]]
+[[Category: Lin W]]

5uh5

From Proteopedia

Current revision

Crystal structure of Mycobacterium tuberculosis transcription initiation complex containing 3 nt of RNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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