5MXK

Structure of Mycobacterium Tuberculosis Transcriptional Regulatory Repressor Protein (EthR) in complex with fragment 7G9.

5MXK の概要

• エントリーDOI: 10.2210/pdb5mxk/pdb
• 分子名称: HTH-type transcriptional regulator EthR, ~{N}-(5-oxidanylidene-7,8-dihydro-6~{H}-naphthalen-2-yl)ethanamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: ethr, repressor, tetr, mycobacterium tuberculosis, transcription
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24109.08

構造登録者

Mendes, V.,Chan, D.S.-H.,Thomas, S.E.,McConnell, B.,Matak-Vinkovic, D.,Coyne, A.G.,Abell, C.,Blundell, T.L. (登録日: 2017-01-23, 公開日: 2017-05-31, 最終更新日: 2024-01-17)

主引用文献

Chan, D.S.,Mendes, V.,Thomas, S.E.,McConnell, B.N.,Matak-Vinkovic, D.,Coyne, A.G.,Blundell, T.L.,Abell, C.
Fragment Screening against the EthR-DNA Interaction by Native Mass Spectrometry.
Angew. Chem. Int. Ed. Engl., 56:7488-7491, 2017

PubMed Abstract: Native nanoelectrospray ionization mass spectrometry is an underutilized technique for fragment screening. In this study, the first demonstration is provided of the use of native mass spectrometry for screening fragments against a protein-DNA interaction. EthR is a transcriptional repressor of EthA expression in Mycobacterium tuberculosis (Mtb) that reduces the efficacy of ethionamide, a second-line antitubercular drug used to combat multidrug-resistant Mtb strains. A small-scale fragment screening campaign was conducted against the EthR-DNA interaction using native mass spectrometry, and the results were compared with those from differential scanning fluorimetry, a commonly used primary screening technique. Hits were validated by surface plasmon resonance and X-ray crystallography. The screening campaign identified two new fragments that disrupt the EthR-DNA interaction in vitro (IC =460-610 μm) and bind to the hydrophobic channel of the EthR dimer.

PubMed: 28513917
DOI: 10.1002/anie.201702888

実験手法

X-RAY DIFFRACTION (1.932 Å)