5C6P

protein C

Summary for 5C6P

• Entry DOI: 10.2210/pdb5c6p/pdb
• Related: 5C6N 5C6O
• Descriptor: protein C, protein D, (2S)-2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile (3 entities in total)
• Functional Keywords: protein, transport protein
• Biological source: Neisseria gonorrhoeae (strain ATCC 700825 / FA 1090); More
• Total number of polymer chains: 2
• Total formula weight: 61089.17

Authors

Lu, M. (deposition date: 2015-06-23, release date: 2015-09-23, Last modification date: 2024-03-06)

Primary citation

Radchenko, M.,Symersky, J.,Nie, R.,Lu, M.
Structural basis for the blockade of MATE multidrug efflux pumps.
Nat Commun, 6:7995-7995, 2015

PubMed 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.

PubMed: 26246409
DOI: 10.1038/ncomms8995

Experimental method

X-RAY DIFFRACTION (3 Å)