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| | ==Crystal structure of Mycobacterium tuberculosis transcription initiation complex== | | ==Crystal structure of Mycobacterium tuberculosis transcription initiation complex== |
| - | <StructureSection load='5uha' size='340' side='right' caption='[[5uha]], [[Resolution|resolution]] 3.91Å' scene=''> | + | <StructureSection load='5uha' size='340' side='right'caption='[[5uha]], [[Resolution|resolution]] 3.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uha]] is a 8 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=5UHA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UHA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uha]] is a 8 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=5UHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UHA 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]] 3.906Å</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]], [[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=5uha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uha OCA], [https://pdbe.org/5uha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uha RCSB], [https://www.ebi.ac.uk/pdbsum/5uha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uha 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=5uha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uha OCA], [http://pdbe.org/5uha PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uha RCSB], [http://www.ebi.ac.uk/pdbsum/5uha PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uha ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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/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/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/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/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> |
| - | <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.
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| - | 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>
| + | ==See Also== |
| - | | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | *[[Sigma factor 3D structures|Sigma factor 3D structures]] |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5uha" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed RNA polymerase]] | + | [[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]]
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| - | [[Category: Rna]]
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| - | [[Category: Rna polymerase complex]]
| + | |
| - | [[Category: Transcription]]
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| - | [[Category: Transcription-dna complex]]
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