7JK8

EmrE S64V mutant bound to tetra(4-fluorophenyl)phosphonium at pH 5.8

7JK8 の概要

• エントリーDOI: 10.2210/pdb7jk8/pdb
• NMR情報: BMRB: 50411
• 分子名称: Multidrug SMR transporter, tetrakis(4-fluorophenyl)phosphanium (2 entities in total)
• 機能のキーワード: small multidrug resistance protein, antiporter, drug efflux pump, membrane protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24362.01

構造登録者

Shcherbakov, A.A.,Hisao, G.,Mandala, V.S.,Thomas, N.E.,Soltani, M.,Salter, E.A.,Davis Jr., J.H.,Henzler-Wildman, K.A.,Hong, M. (登録日: 2020-07-27, 公開日: 2020-12-09, 最終更新日: 2024-05-01)

主引用文献

Shcherbakov, A.A.,Hisao, G.,Mandala, V.S.,Thomas, N.E.,Soltani, M.,Salter, E.A.,Davis Jr., J.H.,Henzler-Wildman, K.A.,Hong, M.
Structure and dynamics of the drug-bound bacterial transporter EmrE in lipid bilayers.
Nat Commun, 12:172-172, 2021

PubMed Abstract: The dimeric transporter, EmrE, effluxes polyaromatic cationic drugs in a proton-coupled manner to confer multidrug resistance in bacteria. Although the protein is known to adopt an antiparallel asymmetric topology, its high-resolution drug-bound structure is so far unknown, limiting our understanding of the molecular basis of promiscuous transport. Here we report an experimental structure of drug-bound EmrE in phospholipid bilayers, determined using F and H solid-state NMR and a fluorinated substrate, tetra(4-fluorophenyl) phosphonium (F-TPP). The drug-binding site, constrained by 214 protein-substrate distances, is dominated by aromatic residues such as W63 and Y60, but is sufficiently spacious for the tetrahedral drug to reorient at physiological temperature. F-TPP lies closer to the proton-binding residue E14 in subunit A than in subunit B, explaining the asymmetric protonation of the protein. The structure gives insight into the molecular mechanism of multidrug recognition by EmrE and establishes the basis for future design of substrate inhibitors to combat antibiotic resistance.

PubMed: 33420032
DOI: 10.1038/s41467-020-20468-7

実験手法

SOLID-STATE NMR