Pandinotoxin
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Pandinotoxin
Pandinotoxins are toxins from the venom of the emperor scorpion '' Pandinus imperator''. They are selective blockers of voltage-gated potassium channels Sources The source for the pandinotoxins is the venom of the scorpion '' Pandinus imperator''. Chemistry Family The toxins of the family are designated pandinotoxin (PiTX)-Kα, PiTX-Kβ, and PiTX-Kγ They are members of the α-KTx family of scorpion toxins. Structure and homology Pandinotoxin Kα and -β The amino acid sequences of PiTX-K α and PiTX-K β are identical, except for the seventh amino acid: a proline in PiTX-Kα and a glutamic acid in PiTX-Kβ (see Fig.1). PiTX-Kα and PiTX-Kβ are 35-residue peptides, which are found to have an α-helix from residues 10 to 21 and two β-sheets (β 1 is from residues 26-28, β 2 is from residues 33-35). One face of the α-helix is anchored to the β-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin family (R-K toxins). PiTX-K α and PiT ...
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KCNA2
Potassium voltage-gated channel subfamily A member 2 also known as Kv1.2 is a protein that in humans is encoded by the ''KCNA2'' gene. Function Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of thi ...
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Shaker Gene
The ''shaker (Sh)'' gene, when mutated, causes a variety of atypical behaviors in the fruit fly, ''Drosophila melanogaster''. Under ether anesthesia, the fly’s legs will shake (hence the name); even when the fly is unanaesthetized, it will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan than regular flies; in their larvae, the repetitive firing of action potentials as well as prolonged exposure to neurotransmitters at neuromuscular junctions occurs. In ''Drosophila'', the shaker gene is located on the X chromosome. The closest human homolog is KCNA3. Function The ''Sh'' gene plays a part in the operation of potassium ion channels, which are integral membrane proteins and are essential to the correct functioning of the cell. A working shaker channel is voltage-dependent and has four subunits, which form a pore through which ions flow, carrying type-A potassium current (IA). A mutation in the Sh gene reduces the conductance of charge across the neuron si ...
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Lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chain lysyl ((CH2)4NH2), classifying it as a basic, charged (at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the ''S'' configuration. The human body cannot synthesize lysine. It is essential in humans and must therefore be obtained from the diet. In organisms that synthesise lysine, two main biosynthetic pathways exist, the diaminopimelate and α-aminoadipate pathways, which employ distinct e ...
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Neurotoxins
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nervous tissue.Olney 2002 The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol (drinking alcohol), glutamate,Choi 1987 nitric oxide, botulinum toxin (e.g. Botox), tetanus toxin,Simpson 1986 and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations. Neurotoxins inhibit neuron control over ion concentrations across the cell membrane, or c ...
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Nociception
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response. In nociception, intense chemical (e.g., capsaicin present in Chili pepper or Cayenne pepper), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory neurons called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses to protect the organism against an aggression and usually results in a subjective experience, or perception, of pain in sentient beings. Detection of noxious stimuli Potentially damaging mechanical, thermal, and chemical stimuli are detected ...
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Hyperalgesia
Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can cause hypersensitivity to stimulus. Prostaglandins E and F are largely responsible for sensitizing the nociceptors. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection. Types Hyperalgesia can be experienced in focal, discrete areas, or as a more diffuse, body-wide form. Conditioning studies have established that it is possible to experience a learned hyperalgesia of the latter, diffuse form. The focal form is typically associated with injury, and is divided into two subtypes: * ''Primary hyperalgesia'' describes pain sensitivity that occurs directly in the damaged tissues. * ''Secondary hyperalgesia'' describes pain sensitivity that occurs in surrounding undamaged tissues. ...
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Allodynia
Allodynia is a condition in which pain is caused by a stimulus that does not normally elicit pain. For example, bad sunburn can cause temporary allodynia, and touching sunburned skin, or running cold or warm water over it, can be very painful. It is different from hyperalgesia, an exaggerated response from a normally painful stimulus. The term is from Ancient Greek '' άλλος'' ''állos'' "other" and '' οδύνη'' ''odúnē'' "pain". Types There are different kinds or types of allodynia: * Mechanical allodynia (also known as tactile allodynia) ** Static mechanical allodynia – pain in response when touched ** Dynamic mechanical allodynia – pain in response to stroking lightly * Thermal (hot or cold) allodynia – pain from normally mild skin temperatures in the affected area * Movement allodynia – pain triggered by normal movement of joints or muscles Causes Allodynia is a clinical feature of many painful conditions, such as neuropathies,Landerholm, A. (2010). Neuropathic ...
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Diclofenac
Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, or applied to the skin. Improvements in pain last for as much as eight hours. It is also available in combination with misoprostol in an effort to decrease stomach problems. Common side effects include abdominal pain, gastrointestinal bleeding, nausea, dizziness, headache, and swelling. Serious side effects may include heart disease, stroke, kidney problems, and stomach ulceration. Use is not recommended in the third trimester of pregnancy. It is likely safe during breastfeeding. Diclofenac is believed to work by decreasing the production of prostaglandins, like other drugs in this class. Diclofenac was patented in 1965 by J.R. Geigy AG; it came into medical use in the United States in 1988. It is available as a generic medication. In ...
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Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure. Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association or docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of lig ...
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Side Chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a larger hydrocarbon backbone. It is one factor in determining a molecule's properties and reactivity. A side chain is also known as a pendant chain, but a pendant group (side group) has a different definition. Conventions The placeholder R is often used as a generic placeholder for alkyl (saturated hydrocarbon) group side chains in chemical structure diagrams. To indicate other non-carbon groups in structure diagrams, X, Y, or Z are often used. History The ''R'' symbol was introduced by 19th-century French chemist Charles Frédéric Gerhardt, who advocated its adoption on the grounds that it would be widely recognizable and intelligible given its correspondence in multiple European languages to the initial letter of "root" or "residue": ...
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Backbone Chain
In polymer science, the polymer chain or simply backbone of a polymer is the main chain of a polymer. Polymers are often classified according to the elements in the main chains. The character of the backbone, i.e. its flexibility, determines the properties of the polymer (such as the glass transition temperature). For example, in polysiloxanes (silicone), the backbone chain is very flexible, which results in a very low glass transition temperature of . The polymers with rigid backbones are prone to crystallization (e.g. polythiophenes) in thin films and in solution. Crystallization in its turn affects the optical properties of the polymers, its optical band gap and electronic levels. Organic polymers : Common synthetic polymers have main chains composed of carbon, i.e. C-C-C-C.... Examples include polyolefins such as polyethylene ((CH2CH2)n) and many substituted derivative ((CH2CH(R))n) such as polystyrene (R = C6H5), polypropylene (R = CH3), and acrylates (R = CO2R'). O ...
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Ion Channels
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters. The study of ion channels often involves biophysics, electrophysiology, and pharmacology, while using techniques including voltage clamp, patch clamp, immunohistochemistry, X-ray crystallography, fluoroscopy, and RT-PCR. Their classification as molecules is referred to as channelomics. Basic features There are two distinctive features of ion channels that differentiate them from other types of ion transporter proteins: #The rate of ion transport through the ...
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