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| | ==X-ray crystal structure of the Escherichia coli RNA polymerase in complex with Benzoxazinorifamycin-2c== | | ==X-ray crystal structure of the Escherichia coli RNA polymerase in complex with Benzoxazinorifamycin-2c== |
| - | <StructureSection load='4kn7' size='340' side='right' caption='[[4kn7]], [[Resolution|resolution]] 3.69Å' scene=''> | + | <StructureSection load='4kn7' size='340' side='right'caption='[[4kn7]], [[Resolution|resolution]] 3.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kn7]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KN7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KN7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kn7]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KN7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KN7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1RM:BENZOXAZINORIFAMYCIN-2C'>1RM</scene>, <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]] 3.686Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kmu|4kmu]], [[4kn4|4kn4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1RM:BENZOXAZINORIFAMYCIN-2C'>1RM</scene>, <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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]), rpoB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]), rpoC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]), rpoZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]), rpoD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</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=4kn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kn7 OCA], [https://pdbe.org/4kn7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kn7 RCSB], [https://www.ebi.ac.uk/pdbsum/4kn7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kn7 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=4kn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kn7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kn7 RCSB], [http://www.ebi.ac.uk/pdbsum/4kn7 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4kn7" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[RNA polymerase|RNA polymerase]] | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| | + | *[[Sigma factor 3D structures|Sigma factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed RNA polymerase]] | |
| | [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
| - | [[Category: Murakami, K S]] | + | [[Category: Large Structures]] |
| - | [[Category: Dna]] | + | [[Category: Murakami KS]] |
| - | [[Category: Rna]]
| + | |
| - | [[Category: Transcription]]
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| - | [[Category: Transferase-antibiotic complex]]
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| Structural highlights
Function
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]
Publication Abstract from PubMed
Rifampin, a semisynthetic rifamycin, is the cornerstone of current tuberculosis treatment. Among many semisynthetic rifamycins, benzoxazinorifamycins have great potential for TB treatment due to their superior affinity for wild-type and rifampin-resistant Mycobacterium tuberculosis RNA polymerases and their reduced hepatic Cyp450 induction activity. In this study, we have determined the crystal structures of the Escherichia coli RNA polymerase complexes with two benzoxazinorifamycins. The ansa-naphthalene moieties of the benzoxazinorifamycins bind in a deep pocket of the beta subunit, blocking the path of the RNA transcript. The C3'-tail of benzoxazinorifamycin fits a cavity between the beta subunit and sigma factor. We propose that in addition to blocking RNA exit, the benzoxazinorifamycin C3'-tail changes the sigma region 3.2 loop position, which influences the template DNA at the active site, thereby reducing the efficiency of transcription initiation. This study supports expansion of structure-activity relationships of benzoxazinorifamycins inhibition of RNA polymerase toward uncovering superior analogues with development potential.
X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins.,Molodtsov V, Nawarathne IN, Scharf NT, Kirchhoff PD, Showalter HD, Garcia GA, Murakami KS J Med Chem. 2013 Jun 13;56(11):4758-63. doi: 10.1021/jm4004889. Epub 2013 May 31. PMID:23679862[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Molodtsov V, Nawarathne IN, Scharf NT, Kirchhoff PD, Showalter HD, Garcia GA, Murakami KS. X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins. J Med Chem. 2013 Jun 13;56(11):4758-63. doi: 10.1021/jm4004889. Epub 2013 May 31. PMID:23679862 doi:10.1021/jm4004889
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