9BFN

Cryo-EM co-structure of AcrB with the CU232 efflux pump inhibitor

これはPDB形式変換不可エントリーです。

9BFN の概要

• エントリーDOI: 10.2210/pdb9bfn/pdb
• EMDBエントリー: 44501
• 分子名称: Multidrug efflux pump subunit AcrB, 1,2-Distearoyl-sn-glycerophosphoethanolamine, (2R)-1-(4-aminopiperidin-1-yl)-3-[3-(trifluoromethyl)phenoxy]propan-2-ol, ... (4 entities in total)
• 機能のキーワード: acrb multidrug efflux pump, translocase
• 由来する生物種: Escherichia coli K-12
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 342810.01

構造登録者

Su, C.C. (登録日: 2024-04-18, 公開日: 2024-05-08)

主引用文献

Allgood, S.C.,Su, C.C.,Crooks, A.L.,Meyer, C.T.,Zhou, B.,Betterton, M.D.,Barbachyn, M.R.,Yu, E.W.,Detweiler, C.S.
Bacterial efflux pump modulators prevent bacterial growth in macrophages and under broth conditions that mimic the host environment.
mBio, 14:e0249223-, 2023

PubMed Abstract: Bacterial efflux pumps are critical for resistance to antibiotics and for virulence. We previously identified small molecules that inhibit efflux pumps (efflux pump modulators, EPMs) and prevent pathogen replication in host cells. Here, we used medicinal chemistry to increase the activity of the EPMs against pathogens in cells into the nanomolar range. We show by cryo-electron microscopy that these EPMs bind an efflux pump subunit. In broth culture, the EPMs increase the potency (activity), but not the efficacy (maximum effect), of antibiotics. We also found that bacterial exposure to the EPMs appear to enable the accumulation of a toxic metabolite that would otherwise be exported by efflux pumps. Thus, inhibitors of bacterial efflux pumps could interfere with infection not only by potentiating antibiotics, but also by allowing toxic waste products to accumulate within bacteria, providing an explanation for why efflux pumps are needed for virulence in the absence of antibiotics.

PubMed: 37921493
DOI: 10.1073/pnas.1901346116

実験手法

ELECTRON MICROSCOPY (2.71 Å)