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排序方式: 共有91条查询结果,搜索用时 31 毫秒
31.
Alpha4/3 conotoxins: phylogenetic distribution, functional properties, and structure-function insights 总被引:1,自引:0,他引:1
This review examines the alpha4/3 conotoxins as an example of molecular diversity in a class of compounds that have evolved in a group of closely related species in a single phylogenetic lineage. The species examined belong to Stephanoconus, a clade of Conus, a genus that contains 500-700 different species of carnivorous marine snails. We examine earlier work that describes the identification and characterization of alpha-ImI, the founding alpha4/3 toxin, and two other alpha4/3 toxins, alpha-ImII and alpha-RgIA. These three toxins all inhibit nicotinic acetylcholine receptors (nAChRs) belonging to a subset of nAChRs that are composed of only alpha subunits; they are, however, diverse in terms of the all-alpha subtype they preferentially antagonize and the receptor site that they bind to. We thus speculate that the alpha4/3 toxins may be a rich source of functionally diverse all-alpha subunit nAChR inhibitors. We review extensive work that has established a detailed model for alpha-ImI binding to one of its preferred nAChR subtypes (the alpha7 nAChR) and, by comparing the alpha-ImI, alpha-ImII and alpha-RgIA sequences demonstrate how structural features of alpha4/3 peptides that account for their diverse functional properties can be identified. This approach is extended to derive models of receptor-toxin binding that may account for the different subtype specificities of alpha4/3 peptides. We also speculate on how rational modification of alpha4/3 toxins may allow engineering of ligands with desired subtype specificities. The chemical diversity produced by the closely related animals in Stephanoconus is thus functionally differentiated, although structurally homologous. 相似文献
32.
Back Cover: A D‐Peptide Ligand of Nicotine Acetylcholine Receptors for Brain‐Targeted Drug Delivery (Angew. Chem. Int. Ed. 10/2015) 下载免费PDF全文
33.
Tamiya N Yagi T 《Proceedings of the Japan Academy. Series B, Physical and biological sciences》2011,87(3):41-52
Erabutoxins a and b are neurotoxins isolated from venom of a sea snake Laticauda semifasciata (erabu-umihebi). Amino acid sequences of the toxins indicated that the toxins are members of a superfamily consisting of short and long neurotoxins and cytotoxins found in sea snakes and terrestrial snakes. The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor on the post synaptic membrane in a manner similar to that of curare. X-ray crystallography and NMR analyses showed that the toxins have a three-finger structure, in which three fingers made of three loops emerging from a dense core make a gently concave surface of the protein. The sequence comparison and the location of essential residues on the protein suggested the mechanism of binding of the toxin to the acetylcholine receptor. Classification of snakes by means of sequence comparison and that based on different morphological features were inconsistent, which led the authors to propose a hypothesis "Evolution without divergence." 相似文献
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35.
《Analytical letters》2012,45(9):1635-1645
Abstract A new receptor based assay is described for the determination of toxins which have high affinities for the acetylcholine receptor. The method is based upon the hindrance of the normal binding of a synthetic enzyme-drug conjugate with a high affinity for the acetylcholine receptor protein by the presence of toxins acting as antagonists. The activity of the enzyme marker system, glucose-6-phosphate dehydrogenase covalently conjugated to desipramine, is monitored by colorimetric detection of the rate for NADH formation at 340 nm. The procedure proposed is designed to provide a simple toxin screen which can be done in a minimally equipped laboratory while achieving the required sensitivity. The technique is illustrated for snake venoms from Bungarus multicintus, Naja naja, and the alkaloid tubocurarine. Aspecific binding responses are shown to have minimal effect on the assay. 相似文献
36.
Rosa Linares Xchitl N. Acua Gabriela Rosas Elizabeth Vieyra Deyra A. Ramírez Andrea Chaparro Julieta A. Espinoza Roberto Domínguez Leticia Morales-Ledesma 《Molecules (Basel, Switzerland)》2021,26(18)
In rats with polycystic ovary syndrome (PCOS) induced by injection of estradiol valerate (EV), unilateral or bilateral section of the vagus nerve restores ovulatory function in 75% of animals, suggesting that the vagus nerve participates in the development of PCOS. Since the vagus nerve is a mixed nerve through which mainly cholinergic-type information passes, the objective of the present study was to analyze whether acetylcholine (ACh) is involved in the development of PCOS. Ten-day-old rats were injected with 2.0 mg EV, and at 60 days of age, they were microinjected on the day of diestrus in the bursa of the left or right ovary with 100 or 700 mg/kg of ovarian weight atropine, a blocker of muscarinic receptors, and sacrificed for histopathological examination after the surgery. Animals with PCOS microinjected with 100 mg of atropine showed a lack of ovulation, lower serum concentrations of progesterone and testosterone, and cysts. Histology of the ovaries of animals microinjected with 700 mg of atropine showed corpus luteum and follicles at different stages of development, which was accompanied by a lower concentration of progesterone and testosterone. These results allow us to suggest that in animals with PCOS, ACh, which passes through parasympathetic innervation, is an important component in the persistence and development of the pathophysiology. 相似文献
37.
Ferdinand Hucho 《Angewandte Chemie (International ed. in English)》1995,34(1):39-50
Neurotoxins have evolved as molecules targeted specifically against molecules with an important function in the nervous system. Because of their selectivity they have been used as probes for detecting and characterizing key proteins of the nerve cell. Ion channels involved in the propagation of the action potential, proteins of presynaptic neurotransmitter exocytosis, and most importantly, neurotransmitter receptors have been and are presently being analyzed, in some cases already at atomic level by a combination of the tools of neurotoxins, molecular biology, and patch clamp electrophysiology. In this review a selection of these toxins is presented, together with their targets in the nervous system. Special emphasis is given to the recent breakthroughs in our understanding of the mechanism of action of tetanus and botulinum toxins and to the neurotoxins ranging from the plant alkaloid strychnine to the peptide toxins from poisonous snakes, which were fundamental in elucidating ligand-gated ion channels like the glycine and nicotinic acetylcholine receptors. 相似文献
38.
Alberto Schena Prof. Kai Johnsson 《Angewandte Chemie (International ed. in English)》2014,53(5):1302-1305
Acetylcholine is a key neurotransmitter, and anticholinesterase agents are essential compounds used as medical drugs, pesticides, and chemical warfare agents. A semisynthetic fluorescence‐based probe for the direct, real‐time detection of acetylcholine and anticholinesterase compounds is introduced. The probe possesses good sensitivity, tunable detection range, and can be selectively targeted to cell surfaces, thereby making it an attractive tool for applications in analytical chemistry and quantitative biology. 相似文献
39.
Miniature endplate potentials (MEPPS) caused by the spontaneous release of ACh from the growth cone of cholinergic neurons, are recorded by the whole-cell patch-clamp technique on a large number of 1-day cultured myoballs which have contact neurites of co-cultured neurons. Both muscle cell and neuron are dissociated from the 1-day-old (about stage 20) Xenopus embryo. Frequency and/or amplitude of MEPPs can obviously increase after the repetitive high-level depolarization caused by the stimuli on muscle cells. No detectable changes of single ACh receptor channel property are observed by using the single-channel recording technique. These results suggest that the mechanism of the increase of MEPPs after electrical activity of postsynaptic muscle cells probably involve some alteration of presynaptic membrane. 相似文献
40.