9 results match your criteria alpha-toxins substitutions

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Key amino acid residues involved in mammalian and insecticidal activities of Magi4 and Hv1b, cysteine-rich spider peptides from the δ-atracotoxin family.

Amino Acids 2020 Mar 17;52(3):465-475. Epub 2020 Feb 17.

Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Apartado Postal 510-3, 62210, Cuernavaca Mor., México.

δ-Atracotoxins, also known as δ-hexatoxins, are spider neurotoxic peptides, lethal to both vertebrates and insects. Their mechanism of action involves the binding to of the S3/S4 loop of the domain IV of the voltage-gated sodium channels (Na). Because of the chemical difficulties of synthesizing folded synthetic δ-atracotoxins correctly, here we explore an expression system that is designed to produce biologically active recombinant δ-atracotoxins, and a number of variants, in order to establish certain amino acids implicated in the pharmacophore of this lethal neurotoxin. Read More

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Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides.

Mol Biol Evol 2016 08 4;33(8):1907-20. Epub 2016 Apr 4.

Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects & Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

Positive selection sites (PSSs), a class of amino acid sites with an excess of nonsynonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e. Read More

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Target-Driven Evolution of Scorpion Toxins.

Sci Rep 2015 Oct 7;5:14973. Epub 2015 Oct 7.

Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects &Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.

It is long known that peptide neurotoxins derived from a diversity of venomous animals evolve by positive selection following gene duplication, yet a force that drives their adaptive evolution remains a mystery. By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex. Despite the lack of positive selection signals in these two loops, they accumulated extensive sequence variations by relaxed purifying selection in prey and predators of scorpions. Read More

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October 2015

Mapping of scorpion toxin receptor sites at voltage-gated sodium channels.

Michael Gurevitz

Toxicon 2012 Sep 4;60(4):502-11. Epub 2012 Apr 4.

Department of Plant Molecular Biology & Ecology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.

Scorpion alpha and beta toxins interact with voltage-gated sodium channels (Na(v)s) at two pharmacologically distinct sites. Alpha toxins bind at receptor site-3 and inhibit channel inactivation, whereas beta toxins bind at receptor site-4 and shift the voltage-dependent activation toward more hyperpolarizing potentials. The two toxin classes are subdivided to distinct pharmacological groups according to their binding preferences and ability to compete for the receptor sites at Na(v) subtypes. Read More

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September 2012

Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion alpha-toxins on sodium channels.

J Biol Chem 2011 Oct 8;286(40):35209-17. Epub 2011 Aug 8.

Department of Plant Molecular Biology and Ecology, George S Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel.

Neurotoxin receptor site-3 at voltage-gated Na(+) channels is recognized by various peptide toxin inhibitors of channel inactivation. Despite extensive studies of the effects of these toxins, their mode of interaction with the channel remained to be described at the molecular level. To identify channel constituents that interact with the toxins, we exploited the opposing preferences of LqhαIT and Lqh2 scorpion α-toxins for insect and mammalian brain Na(+) channels. Read More

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October 2011

Mammalian skeletal muscle voltage-gated sodium channels are affected by scorpion depressant "insect-selective" toxins when preconditioned.

Mol Pharmacol 2007 Nov 24;72(5):1220-7. Epub 2007 Aug 24.

Department of Plant Sciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.

Among scorpion beta- and alpha-toxins that modify the activation and inactivation of voltage-gated sodium channels (Na(v)s), depressant beta-toxins have traditionally been classified as anti-insect selective on the basis of toxicity assays and lack of binding and effect on mammalian Na(v)s. Here we show that the depressant beta-toxins LqhIT2 and Lqh-dprIT3 from Leiurus quinquestriatus hebraeus (Lqh) bind with nanomolar affinity to receptor site 4 on rat skeletal muscle Na(v)s, but their effect on the gating properties can be viewed only after channel preconditioning, such as that rendered by a long depolarizing prepulse. This observation explains the lack of toxicity when depressant toxins are injected in mice. Read More

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November 2007

The unique pharmacology of the scorpion alpha-like toxin Lqh3 is associated with its flexible C-tail.

FEBS J 2007 Apr 9;274(8):1918-31. Epub 2007 Mar 9.

Department of Plant Sciences, George S.Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.

The affinity of scorpion alpha-toxins for various voltage-gated sodium channels (Na(v)s) differs considerably despite similar structures and activities. It has been proposed that key bioactive residues of the five-residue-turn (residues 8-12) and the C-tail form the NC domain, whose topology is dictated by a cis or trans peptide-bond conformation between residues 9 and 10, which correlates with the potency on insect or mammalian Na(v)s. We examined this hypothesis using Lqh3, an alpha-like toxin from Leiurus quinquestriatus hebraeus that is highly active in insects and mammalian brain. Read More

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New toxins acting on sodium channels from the scorpion Leiurus quinquestriatus hebraeus suggest a clue to mammalian vs insect selectivity.

Toxicon 1998 Aug;36(8):1141-54

Laboratoire de Chimie des Biomolecules, URA 1309 CNRS, Institut Pasteur de Lille, France.

Two new toxins were purified from Leiurus quinquestriatus hebraeus (Lqh) scorpion venom, Lqh II and Lqh III. Lqh II sequence reveals only two substitutions, as compared to AaH II, the most active scorpion alpha-toxin on mammals from Androctounus australis Hector. Lqh III shares 80% sequence identity with the alpha-like toxin Bom III from Buthus occitanus mardochei. Read More

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Molecular determinants conferring alpha-toxin resistance in recombinant DNA-derived acetylcholine receptors.

J Biol Chem 1995 Feb;270(8):4165-71

Department of Pharmacology, University of California, La Jolla 92093.

Sequences of the alpha-subunits of the nicotinic acetylcholine receptor from the snake and mongoose contain several differences in the region between amino acids 183 and 200. Receptors from both of these species reveal resistance to the snake alpha-toxins presumably arising as a protective evolutionary mechanism. Sequence differences include the added glycosylation signals at residue 187 in the mongoose and at residues 189 and 111 in snake. Read More

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February 1995
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