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5uhg

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Current revision

Crystal structure of Mycobacterium tuberculosis transcription initiation complex in complex with D-AAP1 and Rifampin

Structural highlights

5uhg is a 8 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	5uh6, 5uh7, 5uh8, 5uh9, 5uha, 5uhb, 5uhc, 5uhd, 5uhe, 5uhf
Gene:	rpoA, Rv3457c, MTCY13E12.10c (MYCTU), rpoB, Rv0667, MTCI376.08c (MYCTU), rpoC, Rv0668, MTCI376.07c (MYCTU), rpoZ, Rv1390, MTCY21B4.07 (MYCTU), sigA, mysA, rpoD, rpoV, Rv2703, MTCY05A6.24 (MYCTU)
Activity:	DNA-directed RNA polymerase, with EC number 2.7.7.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RPOZ_MYCTU] 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.^[1] [RPOA_MYCTU] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059]^[2] [RPOC_MYCTU] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322]^[3] [RPOB_MYCTU] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] [SIGA_MYCTU] 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 (Probable).^[4] ^[5] ^[6]

Publication Abstract from PubMed

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug rifampin (Rif). We report crystal structures of Mtb RNAP, alone and in complex with Rif, at 3.8-4.4 A resolution. The results identify an Mtb-specific structural module of Mtb RNAP and establish that Rif functions by a steric-occlusion mechanism that prevents extension of RNA. We also report non-Rif-related compounds-Nalpha-aroyl-N-aryl-phenylalaninamides (AAPs)-that potently and selectively inhibit Mtb RNAP and Mtb growth, and we report crystal structures of Mtb RNAP in complex with AAPs. AAPs bind to a different site on Mtb RNAP than Rif, exhibit no cross-resistance with Rif, function additively when co-administered with Rif, and suppress resistance emergence when co-administered with Rif.

Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition.,Lin W, Mandal S, Degen D, Liu Y, Ebright YW, Li S, Feng Y, Zhang Y, Mandal S, Jiang Y, Liu S, Gigliotti M, Talaue M, Connell N, Das K, Arnold E, Ebright RH Mol Cell. 2017 Apr 20;66(2):169-179.e8. doi: 10.1016/j.molcel.2017.03.001. Epub, 2017 Apr 6. PMID:28392175^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hu Y, Morichaud Z, Chen S, Leonetti JP, Brodolin K. Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the sigma A-containing RNA polymerase holoenzyme. Nucleic Acids Res. 2012 Aug;40(14):6547-57. doi: 10.1093/nar/gks346. Epub 2012, May 8. PMID:22570422 doi:http://dx.doi.org/10.1093/nar/gks346
↑ Hu Y, Morichaud Z, Chen S, Leonetti JP, Brodolin K. Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the sigma A-containing RNA polymerase holoenzyme. Nucleic Acids Res. 2012 Aug;40(14):6547-57. doi: 10.1093/nar/gks346. Epub 2012, May 8. PMID:22570422 doi:http://dx.doi.org/10.1093/nar/gks346
↑ Hu Y, Morichaud Z, Chen S, Leonetti JP, Brodolin K. Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the sigma A-containing RNA polymerase holoenzyme. Nucleic Acids Res. 2012 Aug;40(14):6547-57. doi: 10.1093/nar/gks346. Epub 2012, May 8. PMID:22570422 doi:http://dx.doi.org/10.1093/nar/gks346
↑ Beaucher J, Rodrigue S, Jacques PE, Smith I, Brzezinski R, Gaudreau L. Novel Mycobacterium tuberculosis anti-sigma factor antagonists control sigmaF activity by distinct mechanisms. Mol Microbiol. 2002 Sep;45(6):1527-40. PMID:12354223
↑ Hartkoorn RC, Sala C, Magnet SJ, Chen JM, Pojer F, Cole ST. Sigma factor F does not prevent rifampin inhibition of RNA polymerase or cause rifampin tolerance in Mycobacterium tuberculosis. J Bacteriol. 2010 Oct;192(20):5472-9. doi: 10.1128/JB.00687-10. Epub 2010 Aug 20. PMID:20729364 doi:http://dx.doi.org/10.1128/JB.00687-10
↑ Hu Y, Morichaud Z, Chen S, Leonetti JP, Brodolin K. Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the sigma A-containing RNA polymerase holoenzyme. Nucleic Acids Res. 2012 Aug;40(14):6547-57. doi: 10.1093/nar/gks346. Epub 2012, May 8. PMID:22570422 doi:http://dx.doi.org/10.1093/nar/gks346
↑ Lin W, Mandal S, Degen D, Liu Y, Ebright YW, Li S, Feng Y, Zhang Y, Mandal S, Jiang Y, Liu S, Gigliotti M, Talaue M, Connell N, Das K, Arnold E, Ebright RH. Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition. Mol Cell. 2017 Apr 20;66(2):169-179.e8. doi: 10.1016/j.molcel.2017.03.001. Epub, 2017 Apr 6. PMID:28392175 doi:http://dx.doi.org/10.1016/j.molcel.2017.03.001

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5uhg"

@@ Line 3: / Line 3: @@
 <StructureSection load='5uhg' size='340' side='right' caption='[[5uhg]], [[Resolution|resolution]] 3.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5uhg]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UHG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5uhg]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UHG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=88G:NALPHA-(BENZENECARBONYL)-N-(2-METHYLPHENYL)-D-PHENYLALANINAMIDE'>88G</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RFP:RIFAMPICIN'>RFP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uh6|5uh6]], [[5uh7|5uh7]], [[5uh8|5uh8]], [[5uh9|5uh9]], [[5uha|5uha]], [[5uhb|5uhb]], [[5uhc|5uhc]], [[5uhd|5uhd]], [[5uhe|5uhe]], [[5uhf|5uhf]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rpoA, Rv3457c, MTCY13E12.10c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), rpoB, Rv0667, MTCI376.08c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), rpoC, Rv0668, MTCI376.07c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), rpoZ, Rv1390, MTCY21B4.07 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), sigA, mysA, rpoD, rpoV, Rv2703, MTCY05A6.24 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=5uhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uhg OCA], [http://pdbe.org/5uhg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uhg RCSB], [http://www.ebi.ac.uk/pdbsum/5uhg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uhg ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 </StructureSection>
 [[Category: DNA-directed RNA polymerase]]
+[[Category: Myctu]]
 [[Category: Das, K]]
 [[Category: Ebright, R H]]

5uhg

From Proteopedia

Current revision

Crystal structure of Mycobacterium tuberculosis transcription initiation complex in complex with D-AAP1 and Rifampin

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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