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| | ==Crystal structure of Escherichia coli RNA polymerase in complex with CBRH16-Br== | | ==Crystal structure of Escherichia coli RNA polymerase in complex with CBRH16-Br== |
| - | <StructureSection load='4zh3' size='340' side='right' caption='[[4zh3]], [[Resolution|resolution]] 4.08Å' scene=''> | + | <StructureSection load='4zh3' size='340' side='right'caption='[[4zh3]], [[Resolution|resolution]] 4.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zh3]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZH3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZH3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zh3]] 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=4ZH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZH3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4OD:N-(3-BROMOPHENYL)-4-FLUORO-N-HYDROXY-3-(TRIFLUOROMETHYL)BENZENECARBOXIMIDAMIDE'>4OD</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]] 4.082Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zh2|4zh2]], [[4zh4|4zh4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OD:N-(3-BROMOPHENYL)-4-FLUORO-N-HYDROXY-3-(TRIFLUOROMETHYL)BENZENECARBOXIMIDAMIDE'>4OD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4zh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zh3 OCA], [https://pdbe.org/4zh3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zh3 RCSB], [https://www.ebi.ac.uk/pdbsum/4zh3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zh3 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=4zh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zh3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zh3 RCSB], [http://www.ebi.ac.uk/pdbsum/4zh3 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == 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/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] |
| | <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 4zh3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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 K-12]] |
| - | [[Category: Ebright, R H]] | + | [[Category: Large Structures]] |
| - | [[Category: Feng, Y]] | + | [[Category: Ebright RH]] |
| - | [[Category: Inhibitor]] | + | [[Category: Feng Y]] |
| - | [[Category: Rna polymerase]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
RPOC_ECOLI DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322]
Publication Abstract from PubMed
CBR hydroxamidines are small-molecule inhibitors of bacterial RNA polymerase (RNAP) discovered through high-throughput screening of synthetic-compound libraries. CBR pyrazoles are structurally related RNAP inhibitors discovered through scaffold hopping from CBR hydroxamidines. CBR hydroxamidines and pyrazoles selectively inhibit Gram-negative bacterial RNAP and exhibit selective antibacterial activity against Gram-negative bacteria. Here, we report crystal structures of the prototype CBR hydroxamidine, CBR703, and a CBR pyrazole in complex with E. coli RNAP holoenzyme. In addition, we define the full resistance determinant for CBR703, show that the binding site and resistance determinant for CBR703 do not overlap the binding sites and resistance determinants of other characterized RNAP inhibitors, show that CBR703 exhibits no or minimal cross-resistance with other characterized RNAP inhibitors, and show that co-administration of CBR703 with other RNAP inhibitors results in additive antibacterial activities. The results set the stage for structure-based optimization of CBR inhibitors as antibacterial drugs.
Structural Basis of Transcription Inhibition by CBR Hydroxamidines and CBR Pyrazoles.,Feng Y, Degen D, Wang X, Gigliotti M, Liu S, Zhang Y, Das D, Michalchuk T, Ebright YW, Talaue M, Connell N, Ebright RH Structure. 2015 Jul 10. pii: S0969-2126(15)00234-8. doi:, 10.1016/j.str.2015.06.009. PMID:26190576[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Feng Y, Degen D, Wang X, Gigliotti M, Liu S, Zhang Y, Das D, Michalchuk T, Ebright YW, Talaue M, Connell N, Ebright RH. Structural Basis of Transcription Inhibition by CBR Hydroxamidines and CBR Pyrazoles. Structure. 2015 Jul 10. pii: S0969-2126(15)00234-8. doi:, 10.1016/j.str.2015.06.009. PMID:26190576 doi:http://dx.doi.org/10.1016/j.str.2015.06.009
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