5uh9

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Crystal structure of Mycobacterium tuberculosis transcription initiation complex containing 2nt RNA

Structural highlights

5uh9 is a 9 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 4.402Å
Ligands:MG, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RPOC_MYCTU DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322][1]

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[2]

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

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Citations
12 reviews cite this structure
Diverse and unified mechanisms of transcription initiation in bacteria.
Chen et al. (2021)
11 more
68 other articles
No citations found

See Also

References

  1. ↑ 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
  2. ↑ 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

Contents


PDB ID 5uh9

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