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Betaine Transporter
The Betaine/Carnitine/Choline Transporter (BCCT) family proteins are found in Gram-negative and Gram-positive bacteria and archaea. The BCCT family members a large group of secondary transporters, the APC superfamily. Their common functional feature is that they all transport molecules with a quaternary ammonium group -N (CH3)3 The BCCT family proteins vary in length between 481 and 706 amino acyl residues and possess 12 putative transmembrane α-helical spanners (TMSs). The x-ray structures reveal two 5 TMS repeats, with the total TMSs being 10. These porters catalyze bidirectional uniport or are energized by pmf-driven or smf-driven proton or sodium ion symport, respectively, or substrate: substrate antiport. Some of these permeases exhibit osmosensory and osmoregulatory properties inherent to their polypeptide chains. Structure The structures of the sodium-independent carnitine/butyrobetaine antiporter CaiT from ''Proteus mirabilis'' (PmCaiT) () and ''E. coli'' (EcCaiT)( ...
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Protein Data Bank
The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules such as proteins and nucleic acids, which is overseen by the Worldwide Protein Data Bank (wwPDB). This structural data is obtained and deposited by biologists and biochemists worldwide through the use of experimental methodologies such as X-ray crystallography, Nuclear magnetic resonance spectroscopy of proteins, NMR spectroscopy, and, increasingly, cryo-electron microscopy. All submitted data are reviewed by expert Biocuration, biocurators and, once approved, are made freely available on the Internet under the CC0 Public Domain Dedication. Global access to the data is provided by the websites of the wwPDB member organizations (PDBe, PDBj, RCSB PDB, and BMRB). The PDB is a key in areas of structural biology, such as structural genomics. Most major scientific journals and some funding agencies now require scientists to submit their structure data to the PDB. Many other ...
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Sodium- And Chloride-dependent Betaine Transporter
Sodium- and chloride-dependent betaine transporter, also known as Na(+)/Cl(-) betaine/GABA transporter (BGT-1), is a protein that in humans is encoded by the ''SLC6A12'' gene. BGT-1 is predominantly expressed in the liver (hepatocytes). It is also expressed in the kidney where it is regulated by NFAT5 during a response to osmotic stress. Further, BGT1 is also present in the leptomeninges surrounding the brain. Deletion of the BGT1 gene in mice did not appear to have any impact on the tendency to develop epilepsy. This is to be expected considering that BGT1 is expressed at far lower levels than GAT1 and also has lower affinity for GABA. This implies that it is not likely to contribute significantly to the inactivation of the inhibitory neurotransmitter GABA. See also * Solute carrier family The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC ge ...
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Integral Membrane Proteins
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a significant fraction of the proteins encoded in an organism's genome. Proteins that cross the membrane are surrounded by annular lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can only be separated from the membranes by using detergents, nonpolar solvents, or sometimes denaturing agents. Proteins that adhere only temporarily to cellular membranes are known as peripheral membrane proteins. These proteins can either associate with integral membrane proteins, or independently insert in the lipid bilayer in several ways. Structure Three-dimensional structures of ~160 different integral membrane proteins have been determined at atomic resolution by X-ray crystallography or nuc ...
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Transport Proteins
A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within an organism. Transport proteins are vital to the growth and life of all living things. There are several different kinds of transport proteins. Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is, they exist within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion (i.e., passive transport) or active transport. These mechanisms of movement are known as carrier-mediated transport. Each carrier protein is designed to recognize only one substance or one group of very similar substances. R ...
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Membrane Proteins
Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane and can either penetrate the membrane (Transmembrane protein, transmembrane) or associate with one or the other side of a membrane (Integral monotopic protein, integral monotopic). Peripheral membrane proteins are transiently associated with the cell membrane. Membrane proteins are common, and medically important—about a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs. Nonetheless, compared to other classes of proteins, determining membrane protein structures remains a challenge in large part due to the difficulty in establishing experimental conditions that can preserve the correct (Native state, native) Protein structure, conformation of the protein in isolation from its native ...
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Protein Families
A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be confused with family as it is used in taxonomy. Proteins in a family descend from a common ancestor and typically have similar three-dimensional structures, functions, and significant sequence similarity. Sequence similarity (usually amino-acid sequence) is one of the most common indicators of homology, or common evolutionary ancestry. Some frameworks for evaluating the significance of similarity between sequences use sequence alignment methods. Proteins that do not share a common ancestor are unlikely to show statistically significant sequence similarity, making sequence alignment a powerful tool for identifying the members of protein families. Families are sometimes grouped together into larger clades called superfamilies based on stru ...
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Protein Domains
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins. Background The concept of the domain was first proposed in 1973 by Wetlaufer after ...
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Transporter Classification Database
The Transporter Classification Database (or TCDB) is an International Union of Biochemistry and Molecular Biology (IUBMB)-approved classification system for membrane transport proteins, including ion channels. Classification The upper level of classification and a few examples of proteins with known 3D structure: 1. Channels and pores 1.A α-type channels * 1.A.1 Voltage-gated ion channel superfamily * 1.A.2 Inward-rectifier K+ channel family * 1.A.3 Ryanodine-inositol-1,4,5-trisphosphate receptor Ca2+ channel family * 1.A.4 Transient receptor potential Ca2+ channel family * 1.A.5 Polycystin cation channel family * 1.A.6 Epithelial Na+ channel family * 1.A.7 ATP-gated P2X receptor cation channel family * 1.A.8 Major intrinsic protein superfamily * 1.A.9 Neurotransmitter receptor, Cys loop, ligand-gated ion channel family * 1.A.10 Glutamate-gated ion channel family of neurotransmitter receptors * 1.A.11 Ammonium channel transporter family * 1.A.12 Intracellular chlorid ...
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Choline
Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membranes. Choline is used to synthesize acetylcholine, a neurotransmitter involved in muscle control and numerous functions of the nervous system. Choline is involved in early development of the brain, gene expression, cell membrane Signaling peptide receptor, signaling, and brain metabolism. Although humans synthesize choline in the liver, the amount produced naturally is insufficient to meet cellular functions, requiring that some choline be obtained from foods or dietary supplements. Foods rich in choline include meats, poultry, eggs, and other animal-based products, cruciferous vegetables, beans, nuts, and whole grains. Choline is present in breast milk and is commonly added as an food additive, ingredient to baby foods. Chemistry Choline i ...
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Carnitine
Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for free energy production, and also participates in removing products of metabolism from cells. Given its key metabolic roles, carnitine is concentrated in tissues like skeletal and cardiac muscle that metabolize fatty acids as an energy source. Generally individuals, including strict vegetarians, synthesize enough L-carnitine in vivo. Carnitine exists as one of two stereoisomers: the two enantiomers -carnitine (''S''-(+)-) and -carnitine (''R''-(−)-). Both are biologically active, but only -carnitine naturally occurs in animals, and -carnitine is toxic as it inhibits the activity of the -form. At room temperature, pure carnitine is a whiteish powder, and a water-soluble zwitterion with relatively low toxicity. Derived from amino acids, ...
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Betaine
A betaine () in chemistry is any neutral chemical compound with a positively charged cationic functional group that bears no hydrogen atom, such as a Quaternary ammonium cation, quaternary ammonium or phosphonium cation (generally: Onium compounds, onium ions), and with a negatively charged functional group, such as a carboxylate group that may not be adjacent to the cationic site. Historically, the term was reserved for trimethylglycine (TMG), which is involved in methylation reactions and detoxification of homocysteine. This is a modified amino acid consisting of glycine with three methyl groups serving as methyl donor for various metabolic pathways. Pronunciation The pronunciation of the compound reflects its origin and first isolation from sugar ''beets'' (''Beta vulgaris'' subsp. ''vulgaris''), and does not derive from the Greek letter beta (β). It is commonly pronounced ''beta-INE'' or ''BEE-tayn''. Glycine betaine The original betaine, ''N'',''N'',''N''-trimethyl ...
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Electrochemical Ion Gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts: * The chemical gradient, or difference in solute concentration across a membrane. * The electrical gradient, or difference in charge across a membrane. If there are unequal concentrations of an ion across a permeable membrane, the ion will move across the membrane from the area of higher concentration to the area of lower concentration through simple diffusion. Ions also carry an electric charge that forms an electric potential across a membrane. If there is an unequal distribution of charges across the membrane, then the difference in electric potential generates a force that drives ion diffusion until the charges are balanced on both sides of the membrane. Electrochemical gradients are essential to the operation of batteries and other electrochemical cells, photosynthesis and cellular respiration, and certain other bi ...
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