7OUK

BDM88855 inhibitor bound to the transmembrane domain of AcrB

7OUK の概要

• エントリーDOI: 10.2210/pdb7ouk/pdb
• 分子名称: Multidrug efflux pump subunit AcrB, (2S)-3-hydroxypropane-1,2-diyl didecanoate, DECYLAMINE-N,N-DIMETHYL-N-OXIDE, ... (14 entities in total)
• 機能のキーワード: multidrug efflux pump, membrane protein, transport protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 389723.24

構造登録者

Tam, H.K.,Foong, W.E.,Pos, K.M. (登録日: 2021-06-12, 公開日: 2021-12-29, 最終更新日: 2024-01-31)

主引用文献

Ple, C.,Tam, H.K.,Vieira Da Cruz, A.,Compagne, N.,Jimenez-Castellanos, J.C.,Muller, R.T.,Pradel, E.,Foong, W.E.,Malloci, G.,Ballee, A.,Kirchner, M.A.,Moshfegh, P.,Herledan, A.,Herrmann, A.,Deprez, B.,Willand, N.,Vargiu, A.V.,Pos, K.M.,Flipo, M.,Hartkoorn, R.C.
Pyridylpiperazine-based allosteric inhibitors of RND-type multidrug efflux pumps.
Nat Commun, 13:115-115, 2022

PubMed Abstract: Efflux transporters of the RND family confer resistance to multiple antibiotics in Gram-negative bacteria. Here, we identify and chemically optimize pyridylpiperazine-based compounds that potentiate antibiotic activity in E. coli through inhibition of its primary RND transporter, AcrAB-TolC. Characterisation of resistant E. coli mutants and structural biology analyses indicate that the compounds bind to a unique site on the transmembrane domain of the AcrB L protomer, lined by key catalytic residues involved in proton relay. Molecular dynamics simulations suggest that the inhibitors access this binding pocket from the cytoplasm via a channel exclusively present in the AcrB L protomer. Thus, our work unveils a class of allosteric efflux-pump inhibitors that likely act by preventing the functional catalytic cycle of the RND pump.

PubMed: 35013254
DOI: 10.1038/s41467-021-27726-2

実験手法

X-RAY DIFFRACTION (2.6 Å)