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| | <StructureSection load='5x22' size='340' side='right'caption='[[5x22]], [[Resolution|resolution]] 3.35Å' scene=''> | | <StructureSection load='5x22' size='340' side='right'caption='[[5x22]], [[Resolution|resolution]] 3.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x22]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/"flavobacterium_thermophilum"_yoshida_and_oshima_1971 "flavobacterium thermophilum" yoshida and oshima 1971], [http://en.wikipedia.org/wiki/Thet2 Thet2] and [http://en.wikipedia.org/wiki/Thet8 Thet8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X22 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x22]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus], [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB27 Thermus thermophilus HB27] and [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X22 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2TM:5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]METHYL}PHOSPHORYL]CYTIDINE'>2TM</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]] 3.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x21|5x21]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TM:5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]METHYL}PHOSPHORYL]CYTIDINE'>2TM</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=274 "Flavobacterium thermophilum" Yoshida and Oshima 1971]), sigA, rpoD, TT_C0164 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=262724 THET2])</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=5x22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x22 OCA], [https://pdbe.org/5x22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x22 RCSB], [https://www.ebi.ac.uk/pdbsum/5x22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x22 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=5x22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x22 OCA], [http://pdbe.org/5x22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x22 RCSB], [http://www.ebi.ac.uk/pdbsum/5x22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x22 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RPOC_THET8 RPOC_THET8]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [[http://www.uniprot.org/uniprot/RPOB_THET8 RPOB_THET8]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [[http://www.uniprot.org/uniprot/RPOA_THETH RPOA_THETH]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [[http://www.uniprot.org/uniprot/RPOZ_THET2 RPOZ_THET2]] 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. [[http://www.uniprot.org/uniprot/SIGA_THET2 SIGA_THET2]] 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.[HAMAP-Rule:MF_00963] | + | [https://www.uniprot.org/uniprot/RPOA_THET8 RPOA_THET8] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. |
| | <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: Flavobacterium thermophilum yoshida and oshima 1971]] | |
| - | [[Category: DNA-directed RNA polymerase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thet2]] | + | [[Category: Thermus thermophilus]] |
| - | [[Category: Thet8]] | + | [[Category: Thermus thermophilus HB27]] |
| - | [[Category: Ebright, R]] | + | [[Category: Thermus thermophilus HB8]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Ebright R]] |
| - | [[Category: Primer-dependent initiation]] | + | [[Category: Zhang Y]] |
| - | [[Category: Rna polymerase]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transferase-dna complex]]
| + | |
| Structural highlights
Function
RPOA_THET8 DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
Publication Abstract from PubMed
Drug-resistant bacterial pathogens pose an urgent public-health crisis. Here, we report the discovery, from microbial-extract screening, of a nucleoside-analog inhibitor that inhibits bacterial RNA polymerase (RNAP) and exhibits antibacterial activity against drug-resistant bacterial pathogens: pseudouridimycin (PUM). PUM is a natural product comprising a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 6'-amino-pseudouridine. PUM potently and selectively inhibits bacterial RNAP in vitro, inhibits bacterial growth in culture, and clears infection in a mouse model of Streptococcus pyogenes peritonitis. PUM inhibits RNAP through a binding site on RNAP (the NTP addition site) and mechanism (competition with UTP for occupancy of the NTP addition site) that differ from those of the RNAP inhibitor and current antibacterial drug rifampin (Rif). PUM exhibits additive antibacterial activity when co-administered with Rif, exhibits no cross-resistance with Rif, and exhibits a spontaneous resistance rate an order-of-magnitude lower than that of Rif. PUM is a highly promising lead for antibacterial therapy.
Antibacterial Nucleoside-Analog Inhibitor of Bacterial RNA Polymerase.,Maffioli SI, Zhang Y, Degen D, Carzaniga T, Del Gatto G, Serina S, Monciardini P, Mazzetti C, Guglierame P, Candiani G, Chiriac AI, Facchetti G, Kaltofen P, Sahl HG, Deho G, Donadio S, Ebright RH Cell. 2017 Jun 15;169(7):1240-1248.e23. doi: 10.1016/j.cell.2017.05.042. PMID:28622509[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Maffioli SI, Zhang Y, Degen D, Carzaniga T, Del Gatto G, Serina S, Monciardini P, Mazzetti C, Guglierame P, Candiani G, Chiriac AI, Facchetti G, Kaltofen P, Sahl HG, Deho G, Donadio S, Ebright RH. Antibacterial Nucleoside-Analog Inhibitor of Bacterial RNA Polymerase. Cell. 2017 Jun 15;169(7):1240-1248.e23. doi: 10.1016/j.cell.2017.05.042. PMID:28622509 doi:http://dx.doi.org/10.1016/j.cell.2017.05.042
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