7B8P

Acinetobacter baumannii multidrug transporter AdeB in OOO state

Summary for 7B8P

• Entry DOI: 10.2210/pdb7b8p/pdb
• EMDB information: 12088
• Descriptor: Efflux pump membrane transporter (1 entity in total)
• Functional Keywords: rnd-transporter, multidrug transporter, antibiotic resistance, membrane protein, transport protein
• Biological source: Acinetobacter baumannii (strain AYE)
• Total number of polymer chains: 3
• Total formula weight: 345429.16

Authors

Ornik-Cha, A.,Reitz, J.,Seybert, A.,Frangakis, A.,Pos, K.M. (deposition date: 2020-12-13, release date: 2021-10-20, Last modification date: 2024-07-10)

Primary citation

Ornik-Cha, A.,Wilhelm, J.,Kobylka, J.,Sjuts, H.,Vargiu, A.V.,Malloci, G.,Reitz, J.,Seybert, A.,Frangakis, A.S.,Pos, K.M.
Structural and functional analysis of the promiscuous AcrB and AdeB efflux pumps suggests different drug binding mechanisms.
Nat Commun, 12:6919-6919, 2021

PubMed Abstract: Upon antibiotic stress Gram-negative pathogens deploy resistance-nodulation-cell division-type tripartite efflux pumps. These include a H/drug antiporter module that recognizes structurally diverse substances, including antibiotics. Here, we show the 3.5 Å structure of subunit AdeB from the Acinetobacter baumannii AdeABC efflux pump solved by single-particle cryo-electron microscopy. The AdeB trimer adopts mainly a resting state with all protomers in a conformation devoid of transport channels or antibiotic binding sites. However, 10% of the protomers adopt a state where three transport channels lead to the closed substrate (deep) binding pocket. A comparison between drug binding of AdeB and Escherichia coli AcrB is made via activity analysis of 20 AdeB variants, selected on basis of side chain interactions with antibiotics observed in the AcrB periplasmic domain X-ray co-structures with fusidic acid (2.3 Å), doxycycline (2.1 Å) and levofloxacin (2.7 Å). AdeABC, compared to AcrAB-TolC, confers higher resistance to E. coli towards polyaromatic compounds and lower resistance towards antibiotic compounds.

PubMed: 34824229
DOI: 10.1038/s41467-021-27146-2

Experimental method

ELECTRON MICROSCOPY (3.54 Å)