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Abc Transporter

E Ruzickova, R Janska, P Dolezel, P Mlejnek
In this work we studied clinically relevant interactions between the BH3 mimetics and the ABCB1 and ABCG2 transporters. We observed that the intracellular levels of ABT-263 and ABT-199, but not ABT-737, might be reduced by ABCB1 or ABCG2. Importantly, this effect was proportional to the transporter expression level. High transporter expression levels decreased the intracellular levels of ABT-263 and ABT-199 substantially. Low transporter expression levels, which are clinically relevant, affected the intracellular level of ABT-263 slightly but significantly, however, they failed to decrease the intracellular level of ABT-199 below the control level in parental cells...
December 1, 2017: Die Pharmazie
Estefania Barreto-Ojeda, Valentina Corradi, Ruo-Xu Gu, D Peter Tieleman
P-glycoprotein (P-gp) exports a broad range of dissimilar compounds, including drugs, lipids, and lipid-like molecules. Because of its substrate promiscuity, P-gp is a key player in the development of cancer multidrug resistance. Although P-gp is one of the most studied ABC transporters, the mechanism by which its substrates access the cavity remains unclear. In this study, we perform coarse-grained molecular dynamics simulations to explore possible lipid access pathways in the inward-facing conformation of P-gp embedded in bilayers of different lipid compositions...
February 6, 2018: Journal of General Physiology
Hiroaki Kawano, Katsushiro Miyamoto, Megumi Yasunobe, Masahiro Murata, Eri Yamahata, Ryo Yamaguchi, Yuta Miyaki, Takahiro Tsuchiya, Tomotaka Tanabe, Tatsuya Funahashi, Hiroshi Tsujibo
Vibrio vulnificus, the causative agent of serious, often fatal, infections in humans, requires iron for its pathogenesis. As such, it obtains iron via both vulnibactin and heme-mediated iron-uptake systems. In this study, we identified the heme acquisition system in V. vulnificus M2799. The nucleotide sequences of the genes encoding heme receptors HupA and HvtA and the ATP-binding cassette (ABC) transport system proteins HupB, HupC, and HupD were determined, and then used in the construction of deletion mutants developed from a Δics strain, which could not synthesize vulnibactin...
February 9, 2018: Microbial Pathogenesis
Jelger A Lycklama A Nijeholt, Ruslan Vietrov, Gea K Schuurman-Wolters, Bert Poolman
Solute transport via ABC importers involves receptor-mediated substrate binding, which is followed by ATP-driven translocation of the substrate across the membrane. How these steps are exactly initiated and coupled, and how much ATP it takes to complete a full transport cycle, are subject of debate. Here, we reconstitute the ABC importer GlnPQ in nanodiscs and in proteoliposomes and determine substrate-(in)dependent ATP hydrolysis and transmembrane transport. We determined the conformational states of the substrate-binding domains (SBDs) by single-molecule FRET measurements...
February 9, 2018: Journal of Molecular Biology
Clémentine Fojcik, Pascal Arnoux, Laurent Ouerdane, Marina Aigle, Laura Alfonsi, Elise Borezée-Durant
Staphylococcus aureus expresses the Cnt system implicated in the active transport of trace metals by synthesizing (CntKLM) and exporting (CntE) staphylopine, a metallophore chelating metals and then taken up by an ABC-transporter (CntABCDF). This machinery is encoded in the cntKLMABCDFE operon, preceded by a non-coding region (PcntK), and containing an internal promoter region (PcntA). PcntK comprises a Fur box followed by a Zur box, a sRNA transcription start and a repeated region, while PcntA comprises a Fur box that overlaps a Zur box...
February 12, 2018: Molecular Microbiology
Steve O'Hagan, Marina Wright Muelas, Philip J Day, Emma Lundberg, Douglas B Kell
The expression levels of SLC or ABC membrane transporter transcripts typically differ 100- to 10,000-fold between different tissues. The Gini coefficient characterizes such inequalities and here is used to describe the distribution of the expression of each transporter among different human tissues and cell lines. Many transporters exhibit extremely high Gini coefficients even for common substrates, indicating considerable specialization consistent with divergent evolution. The expression profiles of SLC transporters in different cell lines behave similarly, although Gini coefficients for ABC transporters tend to be larger in cell lines than in tissues, implying selection...
February 5, 2018: Cell Systems
Camille Taccola, Sylvaine Cartot-Cotton, Delphine Valente, Pascal Barneoud, Catherine Aubert, Valérie Boutet, Fabienne Gallen, Murielle Lochus, Sophie Nicolic, Agnès Dodacki, Maria Smirnova, Salvatore Cisternino, Xavier Declèves, Fanchon Bourasset
Efficacy of drugs aimed at treating central nervous system (CNS) disorders rely partly on their ability to cross the cerebral endothelium, also called the blood-brain barrier (BBB), which constitutes the main interface modulating exchanges of compounds between the brain and blood. In this work, we used both, conventional pharmacokinetics (PK) approach and in situ brain perfusion technique to study the blood and brain PK of PKRinh, an inhibitor of the double-stranded RNA-dependent protein kinase (PKR) activation, in mice...
February 7, 2018: European Journal of Pharmaceutical Sciences
Qing Li, Zunfeng Li, Xingxing Li, Liming Xia, Xuan Zhou, Zhihui Xu, Jiahui Shao, Qirong Shen, Ruifu Zhang
Bacillus velezensis strain SQR9 is a well-investigated rhizobacterium with an outstanding ability to colonize roots, enhance plant growth and suppress soil-borne diseases. The recognition that biofilm formation by plant-beneficial bacteria is crucial for their root colonization and function has resulted in increased interest in understanding molecular mechanisms related to biofilm formation. Here, we report that the gene ftsE, encoding the ATP-binding protein of an FtsEX ABC transporter, is required for efficient SQR9 biofilm formation...
February 7, 2018: Research in Microbiology
Haruka Endo, Satomi Adegawa, Shingo Kikuta, Ryoichi Sato
The cadherin-like protein in lepidopteran insects, known as a receptor for Bacillus thuringiensis Cry1A toxins, is a single-pass membrane protein that can be divided into extracellular and intracellular regions. The extracellular region is important for toxin binding and oligomerization, whereas the role of the intracellular region during Cry1A intoxication is unclear. In the present study, we generated a deletion mutant of Bombyx mori cadherin-like protein (BtR175) that lacked the intracellular region to investigate its role in mediating Cry1A toxicity...
February 6, 2018: Insect Biochemistry and Molecular Biology
Zhengrong Yang, Ellen Hildebrandt, Fan Jiang, Andrei A Aleksandrov, Netaly Khazanov, Qingxian Zhou, Jianli An, Andrew T Mezzell, Bala M Xavier, Haitao Ding, John R Riordan, Hanoch Senderowitz, John C Kappes, Christie G Brouillette, Ina L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is an ABC transporter containing two transmembrane domains forming a chloride ion channel, and two nucleotide binding domains (NBD1 and NBD2). CFTR has presented a formidable challenge to obtain monodisperse, biophysically stable protein. Here we report a comprehensive study comparing effects of single and multiple NBD1 mutations on stability of both the NBD1 domain alone and on purified full length human CFTR. Single mutations S492P, A534P, I539T acted additively, and when combined with M470V, S495P, and R555K cumulatively yielded an NBD1 with highly improved structural stability...
February 6, 2018: Biochimica et Biophysica Acta
Yong-Li Luo, Guang-Xu Ma, Yong-Fang Luo, Ce-Yan Kuang, Ai-Yun Jiang, Guo-Qing Li, Rong-Qiong Zhou
Toxocara canis is a zoonotic parasite with worldwide distribution. ATP-binding cassette (ABC) transporters are integral membrane proteins which involve in a range of biological processes in various organisms. In present study, the full-length coding sequence of abcg-5 gene of T. canis (Tc-abcg-5) was cloned and characterized. A 633 aa polypeptide containing two conserved Walker A and Walker B motifs was predicted from a continuous 1902 nt open reading frame. Quantitative real-time PCR was employed to determine the transcriptional levels of Tc-abcg-5 gene in adult male and female worms, which indicated high mRNA level of Tc-abcg-5 in the reproductive tract of adult female T...
February 8, 2018: Parasitology Research
Weihui Xu, Yimin You, Zhigang Wang, Wenjing Chen, Jin Zeng, Xiaosong Zhao, Yunpeng Su
Dibutyl phthalate (DBP) is well known as a high-priority pollutant. This study explored the impacts of DBP on the metabolic pathways of microbes in black soils in the short term (20 days). The results showed that the microbial communities were changed in black soils with DBP. In nitrogen cycling, the abundances of the genes were elevated by DBP. DBP contamination facilitated 3'-phosphoadenosine-5'-phosphosulfate (PAPS) formation, and the gene flux of sulfate metabolism was increased. The total abundances of ABC transporters and the gene abundances of the monosaccharide-transporting ATPases MalK and MsmK were increased by DBP...
February 8, 2018: Scientific Reports
Guillermo Virkel, Mariana Ballent, Carlos Lanusse, Adrian Lifschitz
Unlike physicians, veterinary practitioners must deal with a number of animal species with crucial differences in anatomy, physiology and metabolism. Accordingly, the pharmacokinetic behaviour, the clinical efficacy and the adverse or toxic effects of drugs may differ across domestic animals. Moreover, the use of drugs in food-producing species may impose a risk for humans due to the generation of chemical residues in edible products, a major concern for public health and consumer's safety. As is clearly known in human beings, the ATP binding cassette (ABC) of transport proteins may influence the bioavailability and elimination of numerous drugs and other xenobiotics in domestic animals as well...
January 31, 2018: Current Medicinal Chemistry
Eunsoo Do, Seho Park, Ming-Hui Li, Jia-Mei Wang, Chen Ding, James W Kronstad, Won Hee Jung
Iron-sulfur clusters (ISC) are indispensable cofactors for essential enzymes in various cellular processes. In the model yeast Saccharomyces cerevisiae, the precursor of ISCs is exported from mitochondria via a mitochondrial ABC transporter Atm1 and used for cytosolic and nuclear ISC protein assembly. Although iron homeostasis has been implicated in the virulence of the human fungal pathogen Cryptococcus neoformans, the key components of the ISC biosynthesis pathway need to be fully elucidated. In the current study, a homolog of S...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Sana Belkahla, Abrar Ul Haq Khan, Delphine Gitenay, Catherine Alexia, Claire Gondeau, Dang-Nghiem Vo, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Guillaume Cartron, Javier Hernandez, Martine Daujat-Chavanieu, Nerea Allende-Vega, Martin Villalba Gonzalez
Changes in metabolism require the efflux and influx of a diverse variety of metabolites. The ABC superfamily of transporters regulates the exchange of hundreds of substrates through the impermeable cell membrane. We show here that a metabolic switch to oxidative phosphorylation (OXPHOS), either by treating cells with dichloroacetate (DCA) or by changing the available substrates, reduced expression of ABCB1, ABCC1, ABCC5 and ABCG2 in wild-type p53-expressing cells. This metabolic change reduced histone changes associated to active promoters...
January 2, 2018: Oncotarget
Yunho Lee, Sooyeon Song, Lili Sheng, Lei Zhu, Jun-Seob Kim, Thomas K Wood
Filamentous phage impact biofilm development, stress tolerance, virulence, biofilm dispersal, and colony variants. Previously, we identified 137 Pseudomonas aeruginosa PA14 mutants with more than threefold enhanced and 88 mutants with more than 10-fold reduced biofilm formation by screening 5850 transposon mutants (PLoS Pathogens5: e1000483, 2009). Here, we characterized the function of one of these 225 mutations, dppA1 (PA14_58350), in regard to biofilm formation. DppA1 is a substrate-binding protein (SBP) involved in peptide utilization via the DppBCDF ABC transporter system...
2018: Frontiers in Microbiology
Milan Hano, Lenka Tomášová, Mário Šereš, Lucia Pavlíková, Albert Breier, Zdena Sulová
Multidrug resistance (MDR) is a phenotype of cancer cells with reduced sensitivity to a wide range of unrelated drugs. P-glycoprotein (P-gp)-a drug efflux pump (ABCB1 member of the ABC transporter gene family)-is frequently observed to be a molecular cause of MDR. The drug-efflux activity of P-gp is considered as the underlying mechanism of drug resistance against P-gp substrates and results in failure of cancer chemotherapy. Several pathological impulses such as shortages of oxygen and glucose supply, alterations of calcium storage mechanisms and/or processes of protein N-glycosylation in the endoplasmic reticulum (ER) leads to ER stress (ERS), characterized by elevation of unfolded protein cell content and activation of the unfolded protein response (UPR)...
February 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Debora Afonso Silva Rocha, Leandro Figueira Reis de Sa, Ana Carolina Cartagenes Pinto, Maria de Lourdes Junqueira, Emiliana Mandarano da Silva, Ronaldo Mohana Borges, Antonio Ferreira-Pereira
BACKGROUND: Candida glabrata ranks second in epidemiological surveillance studies, and is considered one of the main human yeast pathogens. Treatment of Candida infections represents a contemporary public health problem due to the limited availability of an antifungal arsenal, toxicity effects and increasing cases of resistance. C. glabrata presents intrinsic fluconazole resistance and is a significant concern in clinical practice and in hospital environments. OBJECTIVE: The aim of this study was to characterise the azole resistance mechanism presented by a C...
February 5, 2018: Memórias do Instituto Oswaldo Cruz
Atanu Banerjee, Abdul Haseeb Shah, Archana Kumari Redhu, Alexis Moreno, Pierre Falson, Rajendra Prasad
Candida drug resistance 1 (Cdr1), a PDR subfamily ABC transporter mediates efflux of xenobiotics in Candida albicans. It is one of the prime factors contributing to multidrug resistance in the fungal pathogen. One hallmark of this transporter is its asymmetric nature, characterized by peculiar alterations in its nucleotide binding domains. As a consequence, there exists only one canonical ATP-binding site while the other is atypical. Here, we report suppressor analysis on the drug-susceptible transmembrane domain mutant V532D that identified the suppressor mutation W1038S, close to the D-loop of the non-catalytic ATP-binding site...
February 1, 2018: Biochimica et Biophysica Acta
Guinever Eustaquio do Imperio, Enrrico Bloise, Mohsen Javam, Phetcharawan Lye, Andrea Constantinof, Caroline Dunk, Fernando Marcos Dos Reis, Stephen James Lye, William Gibb, Tania M Ortiga-Carvalho, Stephen Giles Matthews
BACKGROUND/AIMS: The ATP-binding cassette (ABC) transporters mediate drug biodisposition and immunological responses in the placental barrier. In vitro infective challenges alter expression of specific placental ABC transporters. We hypothesized that chorioamnionitis induces a distinct pattern of ABC transporter expression. METHODS: Gene expression of 50 ABC transporters was assessed using TaqMan® Human ABC Transporter Array, in preterm human placentas without (PTD; n=6) or with histological chorioamnionitis (PTDC; n=6)...
January 29, 2018: Cellular Physiology and Biochemistry
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