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| | ==Crystal structure of CBR 703 bound to Escherichia coli RNA polymerase holoenzyme== | | ==Crystal structure of CBR 703 bound to Escherichia coli RNA polymerase holoenzyme== |
| - | <StructureSection load='4xsx' size='340' side='right' caption='[[4xsx]], [[Resolution|resolution]] 3.71Å' scene=''> | + | <StructureSection load='4xsx' size='340' side='right'caption='[[4xsx]], [[Resolution|resolution]] 3.71Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xsx]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Citrobacter_koseri_(strain_atcc_baa-895_/_cdc_4225-83_/_sgsc4696) Citrobacter koseri (strain atcc baa-895 / cdc 4225-83 / sgsc4696)] and [http://en.wikipedia.org/wiki/Escherichia_coli_o139:h28_(strain_e24377a_/_etec) Escherichia coli o139:h28 (strain e24377a / etec)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XSX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xsx]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Citrobacter_koseri_ATCC_BAA-895 Citrobacter koseri ATCC BAA-895], [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Escherichia_coli_O139:H28_str._E24377A Escherichia coli O139:H28 str. E24377A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XSX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=42S:N-HYDROXY-N-PHENYL-3-(TRIFLUOROMETHYL)BENZENECARBOXIMIDAMIDE'>42S</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]] 3.708Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xsz|4xsz]], [[4xsy|4xsy]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=42S:N-HYDROXY-N-PHENYL-3-(TRIFLUOROMETHYL)BENZENECARBOXIMIDAMIDE'>42S</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=4xsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xsx OCA], [https://pdbe.org/4xsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xsx RCSB], [https://www.ebi.ac.uk/pdbsum/4xsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xsx 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=4xsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xsx OCA], [http://pdbe.org/4xsx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xsx RCSB], [http://www.ebi.ac.uk/pdbsum/4xsx PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RPOZ_CITK8 RPOZ_CITK8]] 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/RPOA_ECO24 RPOA_ECO24]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [[http://www.uniprot.org/uniprot/RPOC_ECO24 RPOC_ECO24]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [[http://www.uniprot.org/uniprot/RPOB_ECO24 RPOB_ECO24]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [[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_ECO24 RPOA_ECO24] 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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| | </div> | | </div> |
| | <div class="pdbe-citations 4xsx" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4xsx" 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: Citrobacter koseri ATCC BAA-895]] |
| - | [[Category: Bae, B]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Darst, S A]] | + | [[Category: Escherichia coli O139:H28 str. E24377A]] |
| - | [[Category: Bacterial rna polymerase antibiotic complex]] | + | [[Category: Large Structures]] |
| - | [[Category: Transcription-antibiotic complex]] | + | [[Category: Bae B]] |
| | + | [[Category: Darst SA]] |
| Structural highlights
Function
RPOA_ECO24 DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
Publication Abstract from PubMed
RNA polymerase inhibitors like the CBR class that target the enzyme's complex catalytic center are attractive leads for new antimicrobials. Catalysis by RNA polymerase involves multiple rearrangements of bridge helix, trigger loop, and active-center side chains that isomerize the triphosphate of bound NTP and two Mg2+ ions from a preinsertion state to a reactive configuration. CBR inhibitors target a crevice between the N-terminal portion of the bridge helix and a surrounding cap region within which the bridge helix is thought to rearrange during the nucleotide addition cycle. We report crystal structures of CBR inhibitor/Escherichia coli RNA polymerase complexes as well as biochemical tests that establish two distinct effects of the inhibitors on the RNA polymerase catalytic site. One effect involves inhibition of trigger-loop folding via the F loop in the cap, which affects both nucleotide addition and hydrolysis of 3'-terminal dinucleotides in certain backtracked complexes. The second effect is trigger-loop independent, affects only nucleotide addition and pyrophosphorolysis, and may involve inhibition of bridge-helix movements that facilitate reactive triphosphate alignment.
CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition.,Bae B, Nayak D, Ray A, Mustaev A, Landick R, Darst SA Proc Natl Acad Sci U S A. 2015 Jul 20. pii: 201502368. PMID:26195788[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bae B, Nayak D, Ray A, Mustaev A, Landick R, Darst SA. CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition. Proc Natl Acad Sci U S A. 2015 Jul 20. pii: 201502368. PMID:26195788 doi:http://dx.doi.org/10.1073/pnas.1502368112
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