6OOM

PROTEIN A

Summary for 6OOM

• Entry DOI: 10.2210/pdb6oom/pdb
• Descriptor: Multidrug transporter MdfA, LAURYL DIMETHYLAMINE-N-OXIDE, PRASEODYMIUM ION, ... (4 entities in total)
• Functional Keywords: complex, transport, transport protein
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 43233.19

Authors

Lu, M. (deposition date: 2019-04-23, release date: 2019-09-04, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)