Nicotinic receptors

The thesis is structured as follows: In Chapter 1, the scientific literature is summarized within the scope of this study. Chapter 2 provides a comprehensive overview of the principles of the applied computational approaches in this study. Chapter 3 identifies the important residues of the LsIA/α7 nAChR complex that affect the interactions between the toxin and the membrane protein due to C-terminal carboxylation of LsIA. The effects of C-terminal modification of LsIA on interactions with α3β2 nAChR, involved in cardiovascular diseases, were also investigated in Chapter 4.

234p runthenight04 02-02-2023 11 3   Download

Heterologous expression of the extracellular domains (ECDs) of the nicotinic acetylcholine receptor (AChR) subunits may give large amounts of proteins for studying the functional and spatial characteristics of their ligand-binding sites. The ECD of the a7 subunit of the homo-oligomeric a7 neuronal AChR appears to be a more suitable object than the ECDs of other heteromeric neuronal or muscle-type AChRs. The rat a7 ECDs (amino-acid residues  1–210) were recently expressed in Escherichia coli as fusion proteins with maltose-binding protein...

9p system191 01-06-2013 38 3   Download

Weak neurotoxins from snake venom are small proteins with five disulfide bonds, which have been shown to be poor bindersof nicotinicacetylcholine receptors.We report on the cloning and sequencing of four cDNAs encoding weak neurotoxins fromNaja sputatrixvenomglands. The protein encoded by one of them, Wntx-5, has been synthesized by solid-phase synthesis and characterized.

10p research12 23-04-2013 44 4   Download

Intraperitoneal injection of choline (30–90 mgÆkg )1 ) produced a dose-dependent increase in serum insulin, glu-cose and choline levels in rats.The increase in serum insulin induced by choline (90 mgÆkg )1 ) was blocked by pretreat-mentwith themuscarinic acetylcholine receptor antagonists, atropine (2 mgÆkg )1 ), pirenzepine (2 mgÆkg )1 ) and 4-diphe-nylacetoxy-N-methylpiperidine (2 mgÆkg )1 ) or the gangli-onic nicotinic receptor antagonist, hexamethonium (15 mgÆkg )1 ).

9p tumor12 20-04-2013 45 3   Download

High-resolution X-ray diffraction structures of integral membrane proteins have revealed various binding modes of lipids, but current spectroscopic studies still use uniform macroscopic binding constants to describe lipid binding. The Adair approach employing microscopic lipid-binding con-stants has previously been taken to explain the enhancement of agonist binding to the nicotinic acetylcholine receptor by general anaesthetics in terms of the competitive displacement of essential lipid activator molecules [Walcher S, Altschuh J & Sandermann H (2001) J. Biol. Chem. 276, 42191–42195]....

8p awards 06-04-2013 56 2   Download

Aedes aegyptikynurenine aminotransferase (AeKAT) catalyzes the irrevers-ible transamination of kynurenine to kynurenic acid, the natural antagonist of NMDA and 7-nicotinic acetycholine receptors. Here, we report the crys-tal structure of AeKAT in its PMP and PLP forms at 1.90 and 1.55 A ˚ , respectively. The structure was solved by a combination of single-wave-length anomalous dispersion and molecular replacement approaches.

9p awards 06-04-2013 38 2   Download

a-Conotoxins that target the neuronal nicotinic acetylcho-line receptor have a range of potential therapeutic applica-tions and are valuable probes for examining receptor subtype selectivity. The three-dimensional structures of about half of the knownneuronal specifica-conotoxins have nowbeendeterminedandhaveaconsensus foldcontaininga helical region braced by two conserved disulfide bonds. These disulfide bonds define the two-loop framework char-acteristic for a-conotoxins, CCXmCXnC, where loop 1 comprisesfourresidues(m¼4) and loop 2 between three and seven residues (n¼3, 6 or 7). ...

7p dell39 03-04-2013 42 4   Download

The high specificity ofa-conotoxins for different neuronal nicotinic acetylcholine receptors makes them important probes for dissecting receptor subtype selectivity. New sequences continue to expand the diversity and utility of the pool of available a-conotoxins. Their identification andcharacterizationdependonasuiteoftechniques with increasing emphasis on mass spectrometry and micro-scale chromatography, which have benefited from recent advances in resolution and capability.

11p dell39 03-04-2013 41 4   Download

Recent and increasing use of computational tools in the field of nicotinic receptors has led to the publication of several models of ligand–receptor interactions. Thesemodels are all basedon the crystal structure at 2.7 A˚ resolutionof aprotein related to the extracellular N-terminus of nicotinic acetyl-choline receptors (nAChRs), the acetylcholine binding pro-tein. In the absence of any X-ray or NMR information on nAChRs, this new structure has provided a reliable alter-native to study the nAChR structure....

8p dell39 03-04-2013 42 4   Download

Cone snails comprise
500 species of venomous molluscs, which have evolved the ability to generate multiple toxins with varied and often exquisite selectivity. One class, the a-conotoxins, is proving to be a powerful tool for the differentiation of nicotinic acetylcholine receptors (nAChRs). These comprise a large family of complex subtypes, whose significance in physiological functions and pathological conditions is increasingly becoming apparent.

15p dell39 03-04-2013 47 4   Download

There is mounting evidence that the vanilloid (capsaicin) receptor; transient receptor potential channel, vanilloid subfamily member 1 (TRPV1), is subjected to multiple interacting levels of control. The first level is by reversible phosphorylation catalyzed by intrinsic kinases (e.g. protein kinase A and C) and phosphatases (e.g. calcineurin), which plays a pivotal role in receptor sensitization vs. tachyphy-laxis.

6p dell39 03-04-2013 45 3   Download

a-Conotoxins are small peptides from cone snail venoms that function as nicotinic acetylcholine receptor (nAChR)-competitive antagonists differenti-ating between nAChR subtypes. Current understanding about the mechan-ism of these selective interactions is based largely on mutational analyses, which identify amino acids in the toxin and nAChR that determine the energetics of ligand binding.

16p inspiron33 26-03-2013 46 5   Download

TheTorpedonicotinic acetylcholine receptor is a heteropentamer (a2bcd)in which structurally homologous subunits assemble to form a central ion pore. Viewed from the synaptic cleft, the likely arrangement of these sub-units isa–c–a–d–blying in an anticlockwise orientation.

11p inspiron33 26-03-2013 29 4   Download

a-Conotoxins from Conussnails are indispensable tools for distinguishing various subtypes of nicotinic acetylcholine receptors (nAChRs), and synthe-sis of a-conotoxin analogs may yield novel antagonists of higher potency and selectivity. We incorporated additional positive charges intoa-conotox-ins and analyzed their binding to nAChRs.

12p inspiron33 25-03-2013 37 5   Download

The nicotinic acetylcholine receptor (AChR) is a ligand-gated ion channel found in muscles and neurons. Muscle AChR, formed by five homologous subunits (a2bcdora2bce), is the major antigen in the autoimmune disease, myasthenia gravis (MG), in which pathogenic autoantibodies bind to, and inactivate, the AChR.

12p inspiron33 25-03-2013 41 2   Download

Nicotinic acetylcholine receptors (nAChRs) are integral membrane proteins and prototypic members of the ligand-gated ion-channel superfamily, which has precursors in the prokaryotic world. They are formed by the assembly of five transmembrane subunits, selected from a pool of 17 homologous polypeptides (a1–10,b1–4,c, d, and e).

47p galaxyss3 21-03-2013 57 6   Download

a-Conotoxins from marine snails are known to be selective and potent competitive antagonists of nicotinic acetylcholine receptors. Here we des-cribe the purification, structural features and activity of two novel toxins, SrIA and SrIB, isolated fromConus spuriuscollected in the Yucatan Chan-nel, Mexico.

14p galaxyss3 21-03-2013 50 5   Download

Iodinated [ 125 I] weak toxin from Naja kaouthia(WTX) cobra venom was injected into mice, and organ-specific binding was monitored. Relatively high levels of [ 125 I]WTX were detected in the adrenal glands. Rat adrenal membranes were therefore used for analysis of [ 125 I]WTX-binding sites.

11p vinaphone15 25-02-2013 32 4   Download

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Investigating the Influence of PFC Transection and Nicotine on Dynamics of AMPA and NMDA Receptors of VTA Dopaminergic Neurons

28p panasonic08 05-01-2012 58 5   Download

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Investigating the Influence of PFC Transection and Nicotine on Dynamics of AMPA and NMDA Receptors of VTA Dopaminergic Neurons

28p panasonic01 12-12-2011 58 5   Download