7CZ9

Crystal structure of multidrug efflux transporter OqxB from Klebsiella pneumoniae

Summary for 7CZ9

• Entry DOI: 10.2210/pdb7cz9/pdb
• Descriptor: Efflux pump membrane transporter, DODECYL-BETA-D-MALTOSIDE, PHOSPHATIDYLETHANOLAMINE, ... (5 entities in total)
• Functional Keywords: multidrug efflux transporter, drug efflux transporter, membrane transporter, rnd transporter, secondary-active transporter, multidrug resistance, membrane protein
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 6
• Total formula weight: 722462.17

Authors

Murakami, S.,Okada, U.,Yamashita, E. (deposition date: 2020-09-07, release date: 2021-09-22, Last modification date: 2023-11-29)

Primary citation

Bharatham, N.,Bhowmik, P.,Aoki, M.,Okada, U.,Sharma, S.,Yamashita, E.,Shanbhag, A.P.,Rajagopal, S.,Thomas, T.,Sarma, M.,Narjari, R.,Nagaraj, S.,Ramachandran, V.,Katagihallimath, N.,Datta, S.,Murakami, S.
Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae.
Nat Commun, 12:5400-5400, 2021

PubMed Abstract: OqxB is an RND (Resistance-Nodulation-Division) efflux pump that has emerged as a factor contributing to the antibiotic resistance in Klebsiella pneumoniae. OqxB underwent horizontal gene transfer and is now seen in other Gram-negative bacterial pathogens including Escherichia coli, Enterobacter cloacae and Salmonella spp., further disseminating multi-drug resistance. In this study, we describe crystal structure of OqxB with n-dodecyl-β-D-maltoside (DDM) molecules bound in its substrate-binding pocket, at 1.85 Å resolution. We utilize this structure in computational studies to predict the key amino acids contributing to the efflux of fluoroquinolones by OqxB, distinct from analogous residues in related transporters AcrB and MexB. Finally, our complementation assays with mutated OqxB and minimum inhibitory concentration (MIC) experiments with clinical isolates of E. coli provide further evidence that the predicted structural features are indeed involved in ciprofloxacin efflux.

PubMed: 34518546
DOI: 10.1038/s41467-021-25679-0

Experimental method

X-RAY DIFFRACTION (1.85 Å)