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| | <StructureSection load='5uh5' size='340' side='right'caption='[[5uh5]], [[Resolution|resolution]] 3.75Å' scene=''> | | <StructureSection load='5uh5' size='340' side='right'caption='[[5uh5]], [[Resolution|resolution]] 3.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uh5]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UH5 FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.746Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uh6|5uh6]], [[5uh7|5uh7]], [[5uh8|5uh8]], [[5uh9|5uh9]], [[5uha|5uha]], [[5uhb|5uhb]], [[5uhc|5uhc]], [[5uhd|5uhd]], [[5uhe|5uhe]], [[5uhf|5uhf]], [[5uhg|5uhg]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rpoA, Rv3457c, MTCY13E12.10c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), rpoB, Rv0667, MTCI376.08c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), rpoC, Rv0668, MTCI376.07c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), rpoZ, Rv1390, MTCY21B4.07 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), sigA, mysA, rpoD, rpoV, Rv2703, MTCY05A6.24 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5uh5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uh5 OCA], [http://pdbe.org/5uh5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uh5 RCSB], [http://www.ebi.ac.uk/pdbsum/5uh5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uh5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RPOC_MYCTU RPOC_MYCTU]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322]<ref>PMID:22570422</ref> [[http://www.uniprot.org/uniprot/RPOB_MYCTU RPOB_MYCTU]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] [[http://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> [[http://www.uniprot.org/uniprot/RPOZ_MYCTU RPOZ_MYCTU]] Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.<ref>PMID:22570422</ref> [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[RNA polymerase|RNA polymerase]] | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| - | *[[Sigma factor|Sigma factor]] | + | *[[Sigma factor 3D structures|Sigma factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed RNA polymerase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Das, K]] | + | [[Category: Das K]] |
| - | [[Category: Ebright, R H]] | + | [[Category: Ebright RH]] |
| - | [[Category: Feng, Y]] | + | [[Category: Feng Y]] |
| - | [[Category: Lin, W]] | + | [[Category: Lin W]] |
| - | [[Category: Dna]]
| + | |
| - | [[Category: Rna]]
| + | |
| - | [[Category: Rna polymerase complex]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription-dna-rna complex]]
| + | |
| Structural highlights
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.
See Also
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
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