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Yakugaku Zasshi : Journal of the... 2021
Topics: ATP-Binding Cassette Transporters; Drug Discovery; Humans; Membrane Transport Proteins; Nucleotide Transport Proteins; Organic Anion Transporters; Organic Cation Transport Proteins; Research; Sodium-Glucose Transporter 2
PubMed: 33790115
DOI: 10.1248/yakushi.20-00204-F -
Clinical Pharmacology and Therapeutics Sep 2022
Topics: Humans; Membrane Transport Proteins; Pharmacokinetics; Pharmacology; Pharmacology, Clinical
PubMed: 35989454
DOI: 10.1002/cpt.2710 -
International Journal of Molecular... Feb 2023The kidney functions not only as a metabolite elimination organ but also plays an important role in pharmacotherapy. The kidney tubule epithelia cells express membrane... (Review)
Review
The kidney functions not only as a metabolite elimination organ but also plays an important role in pharmacotherapy. The kidney tubule epithelia cells express membrane carriers and transporters, which play an important role in drug elimination, and can determine drug nephrotoxicity and drug-drug interactions, as well as constituting direct drug targets. The above aspects of kidney transport proteins are discussed in the review.
Topics: Humans; Membrane Transport Proteins; Kidney; Carrier Proteins; Drug-Related Side Effects and Adverse Reactions; Drug Interactions; Organic Anion Transporters
PubMed: 36769175
DOI: 10.3390/ijms24032856 -
Biomolecules Nov 2019Plastids, organelles that evolved from cyanobacteria via endosymbiosis in eukaryotes, provide carbohydrates for the formation of biomass and for mitochondrial energy... (Review)
Review
Plastids, organelles that evolved from cyanobacteria via endosymbiosis in eukaryotes, provide carbohydrates for the formation of biomass and for mitochondrial energy production to the cell. They generate their own energy in the form of the nucleotide adenosine triphosphate (ATP). However, plastids of non-photosynthetic tissues, or during the dark, depend on external supply of ATP. A dedicated antiporter that exchanges ATP against adenosine diphosphate (ADP) plus inorganic phosphate (Pi) takes over this function in most photosynthetic eukaryotes. Additional forms of such nucleotide transporters (NTTs), with deviating activities, are found in intracellular bacteria, and, surprisingly, also in diatoms, a group of algae that acquired their plastids from other eukaryotes via one (or even several) additional endosymbioses compared to algae with primary plastids and higher plants. In this review, we summarize what is known about the nucleotide synthesis and transport pathways in diatom cells, and discuss the evolutionary implications of the presence of the additional NTTs in diatoms, as well as their applications in biotechnology.
Topics: Biological Evolution; Biological Transport; Biotechnology; Diatoms; Membrane Transport Proteins; Nucleotides
PubMed: 31766535
DOI: 10.3390/biom9120761 -
Nature Communications May 2023The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which...
The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na-dependent Cl/HCO exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl/HCO exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.
Topics: Mice; Animals; Kidney; Membrane Transport Proteins; Acid-Base Equilibrium; Nephrons; Sulfate Transporters; Bicarbonates; Chloride-Bicarbonate Antiporters
PubMed: 37236964
DOI: 10.1038/s41467-023-38562-x -
Chemical Reviews May 2021Bacterial multidrug efflux pumps have come to prominence in human and veterinary pathogenesis because they help bacteria protect themselves against the antimicrobials... (Review)
Review
Bacterial multidrug efflux pumps have come to prominence in human and veterinary pathogenesis because they help bacteria protect themselves against the antimicrobials used to overcome their infections. However, it is increasingly realized that many, probably most, such pumps have physiological roles that are distinct from protection of bacteria against antimicrobials administered by humans. Here we undertake a broad survey of the proteins involved, allied to detailed examples of their evolution, energetics, structures, chemical recognition, and molecular mechanisms, together with the experimental strategies that enable rapid and economical progress in understanding their true physiological roles. Once these roles are established, the knowledge can be harnessed to design more effective drugs, improve existing microbial production of drugs for clinical practice and of feedstocks for commercial exploitation, and even develop more sustainable biological processes that avoid, for example, utilization of petroleum.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Outer Membrane; Drug Resistance, Microbial; Humans; Membrane Transport Proteins
PubMed: 33761243
DOI: 10.1021/acs.chemrev.0c01226 -
Advances in Neurobiology 2023Monoamine transporters (MATs) are targets of a wide range of compounds that have been developed as therapeutic treatments for various neuropsychiatric and... (Review)
Review
Monoamine transporters (MATs) are targets of a wide range of compounds that have been developed as therapeutic treatments for various neuropsychiatric and neurodegenerative disorders such as depression, ADHD, neuropathic pain, anxiety disorders, stimulant use disorders, epilepsy, and Parkinson's disease. The MAT family is comprised of three main members - the dopamine transporter (DAT), the norepinephrine transporter (NET), and the serotonin transporter (SERT). These transporters are through reuptake responsible for the clearance of their respective monoamine substrates from the extracellular space. The determination of X-ray crystal structures of MATs and their homologues bound with various substrates and ligands has resulted in a surge of structure-function-based studies of MATs to understand the molecular basis of transport function and the mechanism of various ligands that ultimately result in their behavioral effects. This review focusses on recent examples of ligand-based structure-activity relationship studies trying to overcome some of the challenges associated with previously developed MAT inhibitors. These studies have led to the discovery of unique and novel structurally diverse MAT ligands including allosteric modulators. These novel molecular scaffolds serve as leads for designing more effective therapeutic interventions by modulating the activities of MATs and ultimately their associated neurotransmission and behavioral effects.
Topics: Humans; Biological Transport; Ligands; Serotonin Plasma Membrane Transport Proteins; Vesicular Monoamine Transport Proteins; Mental Disorders; Drug Discovery
PubMed: 36928847
DOI: 10.1007/978-3-031-21054-9_4 -
Trends in Biochemical Sciences Feb 2024Tripartite ATP-independent periplasmic (TRAP) transporters are nutrient-uptake systems found in bacteria and archaea. These evolutionary divergent transporter systems... (Review)
Review
Tripartite ATP-independent periplasmic (TRAP) transporters are nutrient-uptake systems found in bacteria and archaea. These evolutionary divergent transporter systems couple a substrate-binding protein (SBP) to an elevator-type secondary transporter, which is a first-of-its-kind mechanism of transport. Here, we highlight breakthrough TRAP transporter structures and recent functional data that probe the mechanism of transport. Furthermore, we discuss recent structural and biophysical studies of the ion transporter superfamily (ITS) members and highlight mechanistic principles that are relevant for further exploration of the TRAP transporter system.
Topics: Bacterial Proteins; Membrane Transport Proteins; Carrier Proteins; Bacteria; Biological Transport
PubMed: 38102017
DOI: 10.1016/j.tibs.2023.11.006 -
Neurochemical Research Jan 2022
Topics: Biomedical Research; Cloning, Molecular; Faculty; GABA Plasma Membrane Transport Proteins; Glutamate Plasma Membrane Transport Proteins; History, 20th Century; History, 21st Century
PubMed: 34617187
DOI: 10.1007/s11064-021-03458-z -
Frontiers in Cellular and Infection... 2019
Topics: Bacteria; Bacterial Proteins; Bacterial Secretion Systems; Host-Pathogen Interactions; Membrane Transport Proteins; Protein Transport
PubMed: 32039049
DOI: 10.3389/fcimb.2019.00473