Conformational plasticity across phylogenetic clusters of RND multidrug efflux pumps and its impact on substrate specificity.

Antibiotic efflux plays a key role for the multidrug resistance in Gram-negative bacteria. Multidrug efflux pumps of the resistance nodulation and cell division (RND) superfamily function as part of cell envelope spanning systems and provide resistance to diverse antibiotics. Here, we identify two phylogenetic clusters of RND proteins with conserved binding pocket residues.

Dissection of an ABC transporter LolCDE function analyzed by photo-crosslinking.

The envelope of Escherichia coli contains approximately 100 different species of lipoproteins, most of which are localized to the inner leaflet of the outer membrane. The localization of lipoprotein (Lol) system, consisting of five Lol proteins, is responsible for the trafficking of lipoproteins to the outer membrane. LolCDE binds to lipoproteins destined for the outer membrane and transfers them to the periplasmic chaperone LolA.

Crystal structures of multidrug efflux transporters from suggest details of transport mechanism.

BpeB and BpeF are multidrug efflux transporters from that enable multidrug resistance. Here, we report the crystal structures of BpeB and BpeF at 2.94 Å and 3.

Structural and functional characteristics of the tripartite ABC transporter.

ATP-binding cassette (ABC) transporters are one of the largest protein superfamilies and are found in all living organisms. These transporters use the energy from ATP binding and hydrolysis to transport various substrates. In this review, we focus on the structural and functional aspects of ABC transporters, with special emphasis on type VII ABC transporters, a newly defined class possessing characteristic structures.

Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae.

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.

Tripartite transporters as mechanotransmitters in periplasmic alternating-access mechanisms.

To remove xenobiotics from the periplasmic space, Gram-negative bacteria utilise unique tripartite efflux systems in which a molecular engine in the plasma membrane connects to periplasmic and outer membrane subunits. Substrates bind to periplasmic sections of the engine or sometimes to the periplasmic subunits. Then, the tripartite machines undergo conformational changes that allow the movement of the substrates down the substrate translocation pathway to the outside of the cell.

BpeB, a major resistance-nodulation-cell division transporter from Burkholderia cenocepacia: construct design, crystallization and preliminary structural analysis.

Burkholderia cenocepacia is an opportunistic pathogen that infects cystic fibrosis patients, causing pneumonia and septicemia. B. cenocepacia has intrinsic antibiotic resistance against monobactams, aminoglycosides, chloramphenicol and fluoroquinolones that is contributed by a homologue of BpeB, which is a member of the resistance-nodulation-cell division (RND)-type multidrug-efflux transporters.

Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii.

The MacA-MacB-TolC tripartite complex is a transmembrane machine that spans both plasma membrane and outer membrane and actively extrudes substrates, including macrolide antibiotics, virulence factors, peptides and cell envelope precursors. These transport activities are driven by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. Here, we present the crystal structure of MacB at 3.

Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump.

The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that spans the cell envelope and actively extrudes substrates, including macrolide antibiotics and polypeptide virulence factors. These transport processes are energized by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. We present an electron cryo-microscopy structure of the ABC-type tripartite assembly at near-atomic resolution.

Structural and genomic DNA analysis of the putative TetR transcriptional repressor SCO7518 from Streptomyces coelicolor A3(2).

SCO7518 is a protein of unknown function from Streptomyces coelicolor A3(2) that has been classified into the TetR transcriptional regulator family. In this study, a crystal structure of SCO7518 was determined at 2.29Å resolution.

SCO4008, a putative TetR transcriptional repressor from Streptomyces coelicolor A3(2), regulates transcription of sco4007 by multidrug recognition.

SCO4008 from Streptomyces coelicolor A3(2) is a member of the TetR family. However, its precise function is not yet clear. In this study, the crystal structure of SCO4008 was determined at a resolution of 2.

Structural and functional analysis of the TetR-family transcriptional regulator SCO0332 from Streptomyces coelicolor.

SCO0332 protein is a putative TetR-family transcriptional regulator from Streptomyces coelicolor A3(2). The crystal structure of SCO0332 was determined at 2.25 A resolution by single-wavelength anomalous diffraction (SAD) phasing using the S atoms of the native protein.

The CGL2612 protein from Corynebacterium glutamicum is a drug resistance-related transcriptional repressor: structural and functional analysis of a newly identified transcription factor from genomic DNA analysis.

The emergence of antibiotic-resistant bacteria often causes serious clinical problems. The TetR family is one of the major transcription factor families that regulate expression of genes involved in bacterial antimicrobial resistance systems. CGL2612 protein is a transcription factor newly identified by genomic DNA analysis on Corynebacterium glutamicum, which belongs to the mycolic acid-containing Actinomycetales, including the well known pathogens Corynebacterium diphtheriae and Mycobacterium tuberculosis.