View source for 4mq9


==Crystal structure of Thermus thermophilus RNA polymerase holoenzyme in complex with GE23077==
<StructureSection load='4mq9' size='340' side='right'caption='[[4mq9]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mq9]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Actinomadura_sp. Actinomadura sp.], [http://en.wikipedia.org/wiki/Thet8 Thet8] and [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MQ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MQ9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MB8:(2Z)-2-METHYLBUT-2-ENOIC+ACID'>MB8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QZ:D-ISOSERINE'>0QZ</scene>, <scene name='pdbligand=2RA:3-AMINO-D-ALANINE'>2RA</scene>, <scene name='pdbligand=2TL:D-ALLOTHREONINE'>2TL</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=FGL:2-AMINOPROPANEDIOIC+ACID'>FGL</scene>, <scene name='pdbligand=R2T:BETA,GAMMA-DIHYDROXYGLUTAMINE'>R2T</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RPOD, TTHA0532 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=300852 THET8])</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=4mq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mq9 OCA], [http://pdbe.org/4mq9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mq9 RCSB], [http://www.ebi.ac.uk/pdbsum/4mq9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mq9 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/RPOZ_THET8 RPOZ_THET8]] 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 (By similarity). [[http://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. [[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/Q5SKW1_THET8 Q5SKW1_THET8]] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released (By similarity).[RuleBase:RU000715]  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 (By similarity).[HAMAP-Rule:MF_00963] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Using a combination of genetic, biochemical, and structural approaches, we show that the cyclic-peptide antibiotic GE23077 (GE) binds directly to the bacterial RNA polymerase (RNAP) active-center 'i' and 'i+1' nucleotide binding sites, preventing the binding of initiating nucleotides, and thereby preventing transcription initiation. The target-based resistance spectrum for GE is unusually small, reflecting the fact that the GE binding site on RNAP includes residues of the RNAP active center that cannot be substituted without loss of RNAP activity. The GE binding site on RNAP is different from the rifamycin binding site. Accordingly, GE and rifamycins do not exhibit cross-resistance, and GE and a rifamycin can bind simultaneously to RNAP. The GE binding site on RNAP is immediately adjacent to the rifamycin binding site. Accordingly, covalent linkage of GE to a rifamycin provides a bipartite inhibitor having very high potency and very low susceptibility to target-based resistance. DOI: http://dx.doi.org/10.7554/eLife.02450.001.

GE23077 binds to the RNA polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides.,Zhang Y, Degen D, Ho MX, Sineva E, Ebright KY, Ebright YW, Mekler V, Vahedian-Movahed H, Feng Y, Yin R, Tuske S, Irschik H, Jansen R, Maffioli S, Donadio S, Arnold E, Ebright RH Elife. 2014 Jan 1;3:e02450. doi: 10.7554/eLife.02450. PMID:24755292<ref>PMID:24755292</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4mq9" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase|RNA polymerase]]
*[[Sigma factor|Sigma factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Actinomadura sp]]
[[Category: DNA-directed RNA polymerase]]
[[Category: Large Structures]]
[[Category: Thermus thermophilus]]
[[Category: Thet8]]
[[Category: Arnold, E]]
[[Category: Ebright, R H]]
[[Category: Ho, M X]]
[[Category: Tuske, S]]
[[Category: Zhang, Y]]
[[Category: Dna-directed rna polymerase]]
[[Category: Transcription]]
[[Category: Transferase-antibiotic complex]]