6ZOH

3-Formylrifamycin SV binding to the access pocket of AcrB-G619P_G621P L and T protomers

Summary for 6ZOH

• Entry DOI: 10.2210/pdb6zoh/pdb
• Descriptor: Multidrug efflux pump subunit AcrB, PHOSPHATIDYLETHANOLAMINE, DECANE, ... (14 entities in total)
• Functional Keywords: multidrug efflux pump, membrane protein, transport protein
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 5
• Total formula weight: 390086.14

Authors

Tam, H.K.,Foong, W.E.,Pos, K.M. (deposition date: 2020-07-07, release date: 2021-05-19, Last modification date: 2024-01-31)

Primary citation

Tam, H.K.,Foong, W.E.,Oswald, C.,Herrmann, A.,Zeng, H.,Pos, K.M.
Allosteric drug transport mechanism of multidrug transporter AcrB.
Nat Commun, 12:3889-3889, 2021

PubMed Abstract: Gram-negative bacteria maintain an intrinsic resistance mechanism against entry of noxious compounds by utilizing highly efficient efflux pumps. The E. coli AcrAB-TolC drug efflux pump contains the inner membrane H/drug antiporter AcrB comprising three functionally interdependent protomers, cycling consecutively through the loose (L), tight (T) and open (O) state during cooperative catalysis. Here, we present 13 X-ray structures of AcrB in intermediate states of the transport cycle. Structure-based mutational analysis combined with drug susceptibility assays indicate that drugs are guided through dedicated transport channels toward the drug binding pockets. A co-structure obtained in the combined presence of erythromycin, linezolid, oxacillin and fusidic acid shows binding of fusidic acid deeply inside the T protomer transmembrane domain. Thiol cross-link substrate protection assays indicate that this transmembrane domain-binding site can also accommodate oxacillin or novobiocin but not erythromycin or linezolid. AcrB-mediated drug transport is suggested to be allosterically modulated in presence of multiple drugs.

PubMed: 34188038
DOI: 10.1038/s41467-021-24151-3

Experimental method

X-RAY DIFFRACTION (2.8 Å)