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| - | {{Large structure}}
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| | ==Escherichia coli RNA polymerase and Rifampin complex, RpoB S531L mutant== | | ==Escherichia coli RNA polymerase and Rifampin complex, RpoB S531L mutant== |
| - | <StructureSection load='5ual' size='340' side='right' caption='[[5ual]], [[Resolution|resolution]] 3.89Å' scene=''> | + | <StructureSection load='5ual' size='340' side='right'caption='[[5ual]], [[Resolution|resolution]] 3.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ual]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UAL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ual]] 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=5UAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UAL 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=RFP:RIFAMPICIN'>RFP</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]] 3.887Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uac|5uac]], [[5uag|5uag]], [[5uah|5uah]], [[5uaj|5uaj]], [[5uaq|5uaq]]</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=RFP:RIFAMPICIN'>RFP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5ual FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ual OCA], [https://pdbe.org/5ual PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ual RCSB], [https://www.ebi.ac.uk/pdbsum/5ual PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ual ProSAT]</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=5ual FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ual OCA], [http://pdbe.org/5ual PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ual RCSB], [http://www.ebi.ac.uk/pdbsum/5ual PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ual ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | {{Large structure}} | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RPOZ_ECOLI RPOZ_ECOLI]] 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.[HAMAP-Rule:MF_00366] [[http://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] [[http://www.uniprot.org/uniprot/RPOC_ECOLI RPOC_ECOLI]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322] [[http://www.uniprot.org/uniprot/RPOB_ECOLI RPOB_ECOLI]] 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/RPOD_ECOLI RPOD_ECOLI]] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This is the primary sigma factor of this bacterium. | + | [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;">
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| - | == Publication Abstract from PubMed ==
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| - | 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.
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| - | 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>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| - | <div class="pdbe-citations 5ual" style="background-color:#fffaf0;"></div>
| + | *[[Sigma factor 3D structures|Sigma factor 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed RNA polymerase]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Garcia, G A]] | + | [[Category: Large Structures]] |
| - | [[Category: Molodtsov, V]] | + | [[Category: Garcia GA]] |
| - | [[Category: Murakami, K S]] | + | [[Category: Molodtsov V]] |
| - | [[Category: Scharf, N T]] | + | [[Category: Murakami KS]] |
| - | [[Category: Stefan, M A]] | + | [[Category: Scharf NT]] |
| - | [[Category: Antibiotic]] | + | [[Category: Stefan MA]] |
| - | [[Category: Inhibitor]]
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| - | [[Category: Rifampin]]
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| - | [[Category: Rifamycin]]
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| - | [[Category: Rna polymerase]]
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| - | [[Category: Rpob s531l]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
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| - | [[Category: Tuberculosis]]
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