4ZP2

Crystal structure of E. coli multidrug transporter MdfA in complex with n-dodecyl-N,N-dimethylamine-N-oxide

Summary for 4ZP2

• Entry DOI: 10.2210/pdb4zp2/pdb
• Related: 4zow 4zp0
• Descriptor: Multidrug transporter MdfA, LAURYL DIMETHYLAMINE-N-OXIDE (3 entities in total)
• Functional Keywords: mfs family, multi-drug antiporter, mdfa, cm, transport protein
• Biological source: Escherichia coli (strain K12)
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P0AEY8
• Total number of polymer chains: 1
• Total formula weight: 42920.43

Authors

Zhang, X.C.,Heng, J.,Zhao, Y.,Wang, X. (deposition date: 2015-05-07, release date: 2015-08-19, Last modification date: 2024-03-20)

Primary citation

Heng, J.,Zhao, Y.,Liu, M.,Liu, Y.,Fan, J.,Wang, X.,Zhao, Y.,Zhang, X.C.
Substrate-bound structure of the E. coli multidrug resistance transporter MdfA
Cell Res., 25:1060-1073, 2015

PubMed Abstract: Multidrug resistance is a serious threat to public health. Proton motive force-driven antiporters from the major facilitator superfamily (MFS) constitute a major group of multidrug-resistance transporters. Currently, no reports on crystal structures of MFS antiporters in complex with their substrates exist. The E. coli MdfA transporter is a well-studied model system for biochemical analyses of multidrug-resistance MFS antiporters. Here, we report three crystal structures of MdfA-ligand complexes at resolutions up to 2.0 Å, all in the inward-facing conformation. The substrate-binding site sits proximal to the conserved acidic residue, D34. Our mutagenesis studies support the structural observations of the substrate-binding mode and the notion that D34 responds to substrate binding by adjusting its protonation status. Taken together, our data unveil the substrate-binding mode of MFS antiporters and suggest a mechanism of transport via this group of transporters.

PubMed: 26238402
DOI: 10.1038/cr.2015.94

Experimental method

X-RAY DIFFRACTION (2.2 Å)