6fbv

From Proteopedia

(Difference between revisions)

Current revision

Single particle cryo em structure of Mycobacterium tuberculosis RNA polymerase in complex with Fidaxomicin

6fbv, resolution 3.50Å

Structural highlights

6fbv is a 6 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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
Experimental data:	Check to display Experimental Data
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

Fidaxomicin is an antibacterial drug in clinical use for treatment of Clostridium difficile diarrhea. The active ingredient of fidaxomicin, lipiarmycin A3 (Lpm), functions by inhibiting bacterial RNA polymerase (RNAP). Here we report a cryo-EM structure of Mycobacterium tuberculosis RNAP holoenzyme in complex with Lpm at 3.5-A resolution. The structure shows that Lpm binds at the base of the RNAP "clamp." The structure exhibits an open conformation of the RNAP clamp, suggesting that Lpm traps an open-clamp state. Single-molecule fluorescence resonance energy transfer experiments confirm that Lpm traps an open-clamp state and define effects of Lpm on clamp dynamics. We suggest that Lpm inhibits transcription by trapping an open-clamp state, preventing simultaneous interaction with promoter -10 and -35 elements. The results account for the absence of cross-resistance between Lpm and other RNAP inhibitors, account for structure-activity relationships of Lpm derivatives, and enable structure-based design of improved Lpm derivatives.

Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3).,Lin W, Das K, Degen D, Mazumder A, Duchi D, Wang D, Ebright YW, Ebright RY, Sineva E, Gigliotti M, Srivastava A, Mandal S, Jiang Y, Liu Y, Yin R, Zhang Z, Eng ET, Thomas D, Donadio S, Zhang H, Zhang C, Kapanidis AN, Ebright RH Mol Cell. 2018 Apr 5;70(1):60-71.e15. doi: 10.1016/j.molcel.2018.02.026. Epub, 2018 Mar 29. PMID:29606590^[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, Das K, Degen D, Mazumder A, Duchi D, Wang D, Ebright YW, Ebright RY, Sineva E, Gigliotti M, Srivastava A, Mandal S, Jiang Y, Liu Y, Yin R, Zhang Z, Eng ET, Thomas D, Donadio S, Zhang H, Zhang C, Kapanidis AN, Ebright RH. Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3). Mol Cell. 2018 Apr 5;70(1):60-71.e15. doi: 10.1016/j.molcel.2018.02.026. Epub, 2018 Mar 29. PMID:29606590 doi:http://dx.doi.org/10.1016/j.molcel.2018.02.026

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fbv"

@@ Line 1: / Line 1: @@
 ==Single particle cryo em structure of Mycobacterium tuberculosis RNA polymerase in complex with Fidaxomicin==
-<StructureSection load='6fbv' size='340' side='right'caption='[[6fbv]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+<SX load='6fbv' size='340' side='right' viewer='molstar' caption='[[6fbv]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fbv]] is a 6 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=6FBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FBV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fbv]] is a 6 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=6FBV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6FBV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FI8:Fidaxomicin'>FI8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FI8:Fidaxomicin'>FI8</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, 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=6fbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fbv OCA], [http://pdbe.org/6fbv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fbv RCSB], [http://www.ebi.ac.uk/pdbsum/6fbv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fbv ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6fbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fbv OCA], [http://pdbe.org/6fbv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fbv RCSB], [http://www.ebi.ac.uk/pdbsum/6fbv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fbv ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 ==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/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: DNA-directed RNA polymerase]]
 [[Category: Large Structures]]

6fbv

From Proteopedia

Current revision

Single particle cryo em structure of Mycobacterium tuberculosis RNA polymerase in complex with Fidaxomicin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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