5IPA

Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with (E)-3-(furan-3-yl)-1-(pyrrolidin-1-yl)prop-2-en-1-one at 1.78A resolution

Summary for 5IPA

• Entry DOI: 10.2210/pdb5ipa/pdb
• Descriptor: TetR-family transcriptional regulatory repressor protein, (2E)-3-(furan-3-yl)-1-(pyrrolidin-1-yl)prop-2-en-1-one (3 entities in total)
• Functional Keywords: ethr, transcription, represor, boosting effect
• Biological source: Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)
• Total number of polymer chains: 1
• Total formula weight: 24355.38

Authors

Blaszczyk, M.,Surade, S.,Nikiforov, P.O.,Abell, C.,Blundell, T.L. (deposition date: 2016-03-09, release date: 2017-03-29, Last modification date: 2024-01-10)

Primary citation

Nikiforov, P.O.,Blaszczyk, M.,Surade, S.,Boshoff, H.I.,Sajid, A.,Delorme, V.,Deboosere, N.,Brodin, P.,Baulard, A.R.,Barry, C.E.,Blundell, T.L.,Abell, C.
Fragment-Sized EthR Inhibitors Exhibit Exceptionally Strong Ethionamide Boosting Effect in Whole-Cell Mycobacterium tuberculosis Assays.
ACS Chem. Biol., 12:1390-1396, 2017

PubMed Abstract: Small-molecule inhibitors of the mycobacterial transcriptional repressor EthR have previously been shown to act as boosters of the second-line antituberculosis drug ethionamide. Fragment-based drug discovery approaches have been used in the past to make highly potent EthR inhibitors with ethionamide boosting activity both in vitro and ex vivo. Herein, we report the development of fragment-sized EthR ligands with nanomolar minimum effective concentration values for boosting the ethionamide activity in Mycobacterium tuberculosis whole-cell assays.

PubMed: 28314097
DOI: 10.1021/acschembio.7b00091

Experimental method

X-RAY DIFFRACTION (1.78 Å)