5UH7

Crystal structure of beta'MtbSI of Mycobacterium tuberculosis RNA polymerase

Summary for 5UH7

• Entry DOI: 10.2210/pdb5uh7/pdb
• Related: 5UH6 5UH8 5UHA 5UHB 5UHC 5UHD 5UHE 5UHF 5UHG
• Descriptor: DNA-directed RNA polymerase subunit beta' (2 entities in total)
• Functional Keywords: rna polymerase complex, transcription, dna, rna
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 39025.47

Authors

Lin, W.,Das, K.,Feng, Y.,Ebright, R.H. (deposition date: 2017-01-11, release date: 2017-04-12, Last modification date: 2024-03-06)

Primary citation

Lin, W.,Mandal, S.,Degen, D.,Liu, Y.,Ebright, Y.W.,Li, S.,Feng, Y.,Zhang, Y.,Mandal, S.,Jiang, Y.,Liu, S.,Gigliotti, M.,Talaue, M.,Connell, N.,Das, K.,Arnold, E.,Ebright, R.H.
Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition.
Mol. Cell, 66:169-179.e8, 2017

PubMed Abstract: 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 Å 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-Nα-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.

PubMed: 28392175
DOI: 10.1016/j.molcel.2017.03.001

Experimental method

X-RAY DIFFRACTION (2.199 Å)