6c06

From Proteopedia

(Difference between revisions)

Revision as of 23:32, 10 April 2020

Mycobacterium tuberculosis RNAP Holo/RbpA/Fidaxomicin

6c06, resolution 5.15Å

Structural highlights

6c06 is a 7 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	6bzo, 6c04, 6c05
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

[A0A045IP01_MYCTX] Binds to RNA polymerase (RNAP), stimulating transcription from principal, but not alternative sigma factor promoters.[HAMAP-Rule:MF_01483] [A0A0T9N9K3_MYCTX] 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][SAAS:SAAS00298387] [A0A045J8T1_MYCTX] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059] [A0A045J9E2_MYCTX] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU004279][SAAS:SAAS00365746] [V9Z879_MYCTX] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU363031] [A0A045HD00_MYCTX] 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.[SAAS:SAAS00535554]

Publication Abstract from PubMed

Fidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective against Mycobacterium tuberculosis RNAP in vitro, but clinical use of Fdx is limited to treating Clostridium difficile intestinal infections due to poor absorption. To identify the structural determinants of Fdx binding to RNAP, we determined the 3.4 A cryo-electron microscopy structure of a complete M. tuberculosis RNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin, explaining its strong effect on M. tuberculosis. Additional structures define conformational states of M. tuberculosis RNAP between the free apo-holoenzyme and the promoter-engaged open complex ready for transcription. The results establish that Fdx acts like a doorstop to jam the enzyme in an open state, preventing the motions necessary to secure promoter DNA in the active site. Our results provide a structural platform to guide development of anti-tuberculosis antimicrobials based on the Fdx binding pocket.

Fidaxomicin jams Mycobacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts.,Boyaci H, Chen J, Lilic M, Palka M, Mooney RA, Landick R, Darst SA, Campbell EA Elife. 2018 Feb 26;7. pii: 34823. doi: 10.7554/eLife.34823. PMID:29480804^[1]

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

References

↑ Boyaci H, Chen J, Lilic M, Palka M, Mooney RA, Landick R, Darst SA, Campbell EA. Fidaxomicin jams Mycobacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts. Elife. 2018 Feb 26;7. pii: 34823. doi: 10.7554/eLife.34823. PMID:29480804 doi:http://dx.doi.org/10.7554/eLife.34823

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/6c06"

@@ Line 3: / Line 3: @@
 <SX load='6c06' size='340' side='right' viewer='molstar' caption='[[6c06]], [[Resolution|resolution]] 5.15&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6c06]] is a 7 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C06 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C06 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6c06]] is a 7 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C06 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C06 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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6bzo|6bzo]], [[6c04|6c04]], [[6c05|6c05]]</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=6c06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c06 OCA], [http://pdbe.org/6c06 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c06 RCSB], [http://www.ebi.ac.uk/pdbsum/6c06 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c06 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=6c06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c06 OCA], [http://pdbe.org/6c06 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c06 RCSB], [http://www.ebi.ac.uk/pdbsum/6c06 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c06 ProSAT]</span></td></tr>
 </table>
 == Function ==

6c06

From Proteopedia

Revision as of 23:32, 10 April 2020

Mycobacterium tuberculosis RNAP Holo/RbpA/Fidaxomicin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox