6OOP

protein B

6OOP の概要

• エントリーDOI: 10.2210/pdb6oop/pdb
• 分子名称: Multidrug transporter MdfA, 1,1'-dimethyl-4,4'-bipyridin-1-ium, PRASEODYMIUM ION, ... (4 entities in total)
• 機能のキーワード: complex, transport, transport protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42960.64

構造登録者

Lu, M. (登録日: 2019-04-23, 公開日: 2019-09-04, 最終更新日: 2024-03-13)

主引用文献

Wu, H.H.,Symersky, J.,Lu, M.
Structure of an engineered multidrug transporter MdfA reveals the molecular basis for substrate recognition.
Commun Biol, 2:210-210, 2019

PubMed Abstract: MdfA is a prototypical H-coupled multidrug transporter that is characterized by extraordinarily broad substrate specificity. The involvement of specific H-bonds in MdfA-drug interactions and the simplicity of altering the substrate specificity of MdfA contradict the promiscuous nature of multidrug recognition, presenting a baffling conundrum. Here we show the X-ray structures of MdfA variant I239T/G354E in complexes with three electrically different ligands, determined at resolutions up to 2.2 Å. Our structures reveal that I239T/G354E interacts with these compounds differently from MdfA and that I239T/G354E possesses two discrete, non-overlapping substrate-binding sites. Our results shed new light on the molecular design of multidrug-binding and protonation sites and highlight the importance of often-neglected, long-range charge-charge interactions in multidrug recognition. Beyond helping to solve the ostensible conundrum of multidrug recognition, our findings suggest the mechanistic difference between substrate and inhibitor for any H-dependent multidrug transporter, which may open new vistas on curtailing efflux-mediated multidrug resistance.

PubMed: 31240248
DOI: 10.1038/s42003-019-0446-y

実験手法

X-RAY DIFFRACTION (2.8 Å)