The ABC transporter MsbA is an integral membrane protein involved in the transport of lipid A and lipopolysaccharides to the outer leaflet of the inner membrane in bacteria. Here, the critical role of the natural substrate lipopolysaccharide in the crystallization and diffraction quality of ...
PubMed Central
Bacterial ATP binding cassette (ABC) exporters fulfill a wide variety of transmembrane transport roles and are homologous to the human multidrug resistance P-glycoprotein. Recent x-ray structures of the exporters MsbA and Sav1866 have begun to describe the conformational changes that accompany the ABC ...
Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs and lipids from the inner to the outer ...
E-print Network
ATP-binding cassette (ABC) transporters make up one of the largest classes of proteins found in nature, and their ability to move a variety of substrates across the membrane using energy from the binding or hydrolysis of ATP is essential to an array of human pathologies and to bacterial viability. MsbA is an essential ...
MsbA is a member of the ABC transporter superfamily and is homologous to ABC transporters linked to multidrug resistance. The nucleotide binding domains (NBDs) of these proteins include conserved motifs that are involved in ATP binding, including conserved SALD residues (D-loop) that are ...
PubMed
J. Thomas and John F. Hunt The 4.5 � map of the MsbA protein, a putative lipid A transporter from `loops' of an ABC transporter and the geometric relationship of these regions to the ATP-binding cassette to the other. ATP-binding cas- sette (or ABC) transporters represent ...
MsbA is a member of the ABC transporter superfamily that is specifically found in Gram-negative bacteria and is homologous to proteins involved in both bacterial and human drug resistance. The E506Q and H537A mutations have been introduced and used for crystallization of other members of the ABC ...
ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a wide variety of substrates across cellular membranes and are conserved from bacteria to humans. Here we compare four x-ray structures of the bacterial ABC lipid flippase, MsbA, trapped in different conformations, two ...
Energy Citations Database
ATP binding cassette (ABC) transporters make up one of the largest superfamilies of proteins known and have been shown to transport substrates ranging from lipids and antibiotics to sugars and amino acids. The dysfunction of ABC transporters has been linked to human pathologies such as cystic ...
We measured the amplitude of conformational motion in the ATP-binding cassette (ABC) transporter MsbA upon lipopolysaccharide (LPS) binding and following ATP turnover by pulse double electron-electron resonance and fluorescence homotransfer. The distance constraints from both methods reveal large-scale movement of opposite signs in the ...
The MsbA protein is an essential ABC (ATP-binding-cassette) superfamily member in Gram-negative bacteria. This 65�kDa membrane protein is thought to function as a homodimeric ATP-dependent lipid translocase or flippase that transports lipid A from the inner to the outer leaflet of the cytoplasmic membrane. We have previously shown ...
Driven by the energy of ATP binding and hydrolysis, ATP-binding cassette transporters alternate between inward- and outward-facing conformations, allowing vectorial movement of substrates. Conflicting models have been proposed to describe the conformational motion underlying this switch in access of the transport pathway. One model, based on three crystal ...
Previously published 3-D structures of a prototypic ATP-binding cassette (ABC) transporter, MsbA, have been recently corrected revealing large rigid-body motions possibly linked to its catalytic cycle. Here, a closely related multidrug bacterial ABC transporter, BmrA, was studied using ...
Multidrug resistance protein 1 (MRP1/ABCC1) is a 190 kDa member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that is clinically relevant for its ability to confer multidrug resistance by actively effluxing anticancer drugs. Knowledge of the atomic structure of MRP1 is needed to elucidate its transport ...
Helical crystallization is a powerful tool for the moderate resolution structure determination of integral membrane proteins, where the insight gained often includes domain architecture and the disposition of ?-helical segments. A necessary first step toward helical crystallization involves membrane protein reconstitution, which itself is a powerful technique for structure-function studies of ...
ABC transporters play important roles in all types of organisms by participating in physiological and pathological processes. In order to modulate the function of ABC transporters, detailed knowledge regarding their structure and dynamics is necessary. Available structures of ABC proteins ...
Human multidrug resistance ABC transporters are ubiquitous membrane proteins responsible for the efflux of multiple, endogenous or exogenous, compounds out of the cells, and therefore they are involved in multi-drug resistance phenotype (MDR). They thus deeply impact the pharmacokinetic parameters and toxicity properties of drugs. A great pressure to ...
The human ATP-binding cassette (ABC) transporters ABCB1, ABCC4 and ABCC5 are involved in resistance to chemotherapeutic agents. Here we present molecular models of ABCB1, ABCC4 and ABCC5 by homology based on a wide open inward-facing conformation of Escherichia coli MsbA, which were constructed in order to elucidate differences in the ...
ATP-Binding Cassette (ABC) transporters are efflux pumps frequently associated with multidrug resistance in many biological systems, including malaria. Antimalarial drug-resistance involves an ABC transporter, PfMDR1, a homologue of P-glycoprotein in humans. Twenty years of research have shown that several single ...
We report a significant methodological advance in the application of double electron-electron resonance (DEER) spectroscopy to measure long-range distances in spin-labeled membrane proteins. In the pseudo two-dimensional environment of proteoliposomes, a steep intermolecular background shapes DEER signals leading to long accumulation times, complicating data analysis and reducing the maximal ...
The lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most Gram-negative bacteria. Escherichia coli lipid A is synthesized on the cytoplasmic surface of the inner membrane by a conserved pathway of nine constitutive enzymes. Following attachment of the core oligosaccharide, lipid A is flipped to the outer surface of the inner membrane by the ...
Table 1. Clinically relevant and atypical ABC proteins Kenneth J. Linton. Structure and Function of ABC Transporters. Physiology 22: 122-130, 2007
NSDL National Science Digital Library
Sinorhizobium meliloti produces an exopolysaccharide called succinoglycan that plays a critical role in promoting symbiosis with its host legume, alfalfa (Medicago sativa). We performed a transposon mutagenesis and screened for mutants with altered succinoglycan production and a defect in symbiosis. In this way, we identified a putative two-component histidine kinase associated with a PAS sensory ...
). #12;Chapter 1 2.2. Binding protein dependent ABC- type transporters The sugar transporters characterized so, and Rad50cd, a DNA repair protein which shows ATP-binding domains similar to the domains found in ABC-transporters a binding protein-dependent ATP- binding cassette (ABC)-transporter ...
Advances in understanding the overall structural features of inward rectifiers and ATP-binding cassette (ABC) transporters are providing novel insight into the architecture of ATP-sensitive K+ channels (KATP channels) (KIR6.0/SUR)4. The structure of the K(IR) pore has been modeled on bacterial K+ channels, while the lipid-A exporter, ...
-binding proteins (SBPs) of ATP Binding Cassette (ABC) transporters has been ongoing for at least four decades. Our on the lactococcal oligopeptide binding protein A (OppA), the receptor component of the ABC-transporter oligopeptide picture how these proteins work. Three types of ABC-transporters exist: ...
of SBP-dependent membrane proteins. A-B: visualizes ABC- transporters. A: ABC-importer with the SBP dependent transport proteins ABC-transporters exist in all three kingdom of life and transport a large of the membrane protein. In mGluR this signal is triggered by ligand ...
Etravirine is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infections. ABC transporters potentially mediate clinically relevant drug-drug interactions. We assessed substrate characteristics and the inhibitory and inductive potential of etravirine on ABC transporters. ...
FIGURE 1. The minimal ABC transporter has four domains. Two transmembrane domains (TMDs) bind ligand, and transport is driven by ATP binding and hydrolysis by the two nucleotide binding domains (NBDs). The TMDs from different subfamilies of ABC transporters are not necessarily homologous. The ...
