PDBsum entry 6oop

Transport protein

PDB id: 6oop

Contents

Protein chain

392 a.a.

Ligands

KHJ

Metals

_PR ×2

Waters ×55

PDB id:

6oop

Name:

Transport protein

Title:

Protein b

Structure:

Multidrug transporter mdfa. Chain: a. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: a9r57_05385, bjj90_17655. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.80Å R-factor: not given

Authors:

M.Lu

Key ref:

H.H.Wu et al. (2019). Structure of an engineered multidrug transporter MdfA reveals the molecular basis for substrate recognition. Commun Biol, 2, 210. PubMed id: 31240248 DOI: 10.1038/s42003-019-0446-y

Date:

23-Apr-19 Release date: 04-Sep-19

Protein chain

P0AEY8  (MDFA_ECOLI) -  Multidrug transporter MdfA from Escherichia coli (strain K12)

Seq: 410 a.a.

Struc: 392 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/s42003-019-0446-y

Commun Biol 2:210 (2019)

PubMed id: 31240248

Structure of an engineered multidrug transporter MdfA reveals the molecular basis for substrate recognition.

H.H.Wu, J.Symersky, M.Lu.

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.