PDBsum entry 5c6p

Transport protein

PDB id: 5c6p

Contents

Protein chains

459 a.a.

91 a.a.

Ligands

4YH

PDB id:

5c6p

Name:

Transport protein

Title:

Protein c

Structure:

Protein c. Chain: a. Synonym: putative efflux pump protein. Engineered: yes. Protein d. Chain: b. Engineered: yes

Source:

Neisseria gonorrhoeae (strain atcc 700825 / fa 1090). Organism_taxid: 242231. Strain: atcc 700825 / fa 1090. Gene: ngo0395. Expressed in: escherichia coli. Expression_system_taxid: 562. Escherichia coli. Organism_taxid: 562.

Resolution:

3.00Å R-factor: 0.280 R-free: 0.290

Authors:

M.Lu

Key ref:

M.Radchenko et al. (2015). Structural basis for the blockade of MATE multidrug efflux pumps. Nat Commun, 6, 7995. PubMed id: 26246409 DOI: 10.1038/ncomms8995

Date:

23-Jun-15 Release date: 23-Sep-15

Protein chain

Q5F9J8  (Q5F9J8_NEIG1) -  Multidrug-efflux transporter from Neisseria gonorrhoeae (strain ATCC 700825 / FA 1090)

Seq: 459 a.a.

Struc: 459 a.a.

Protein chain

M1E1G6  (M1E1G6_ECOLX) -  Protein B from Escherichia coli

Seq: 99 a.a.

Struc: 91 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1038/ncomms8995

Nat Commun 6:7995 (2015)

PubMed id: 26246409

Structural basis for the blockade of MATE multidrug efflux pumps.

M.Radchenko, J.Symersky, R.Nie, M.Lu.

ABSTRACT

Multidrug and toxic compound extrusion (MATE) transporters underpin multidrug resistance by using the H(+) or Na(+) electrochemical gradient to extrude different drugs across cell membranes. MATE transporters can be further parsed into the DinF, NorM and eukaryotic subfamilies based on their amino-acid sequence similarity. Here we report the 3.0 Å resolution X-ray structures of a protonation-mimetic mutant of an H(+)-coupled DinF transporter, as well as of an H(+)-coupled DinF and a Na(+)-coupled NorM transporters in complexes with verapamil, a small-molecule pharmaceutical that inhibits MATE-mediated multidrug extrusion. Combining structure-inspired mutational and functional studies, we confirm the biological relevance of our crystal structures, reveal the mechanistic differences among MATE transporters, and suggest how verapamil inhibits MATE-mediated multidrug efflux. Our findings offer insights into how MATE transporters extrude chemically and structurally dissimilar drugs and could inform the design of new strategies for tackling multidrug resistance.