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      Biological and molecular properties of yellow venom of the Amazonian coral snake Micrurus surinamensis

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          Abstract

          Abstract INTRODUCTION: The coral snake Micrurus surinamensis, which is widely distributed throughout Amazonia, has a neurotoxic venom. It is important to characterize the biological and molecular properties of this venom in order to develop effective antitoxins. METHODS: Toxins from the venom of M. surinamensis were analyzed by two-dimensional polyacrylamide gel electrophoresis and their neurotoxic effects in vivo were evaluated. RESULTS AND CONCLUSIONS: Most proteins in the venom had masses < 14kDa, low phospholipase A2 activity, and no proteolytic activity. The toxins inhibited the coagulation cascade. The venom had neurotoxic effects in mice, with a median lethal dose upon intravenous administration of 700 µg/kg. Immunogenic studies revealed abundant cross-reactivity of antielapidic serum with 14kDa toxins and limited cross-reactivity with toxins < 10kDa. These results indicate that antielapidic serum against M. surinamensis venom has weak potency (0.35mg/ml) in mice.

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            Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms.

            R. Kini (2005)
            Phospholipase A(2) (PLA(2)) enzymes from snake venom are toxic and induce a wide spectrum of pharmacological effects, despite similarity in primary, secondary and tertiary structures and common catalytic properties. Thus, the structure-function relationships and the mechanism of this group of small proteins are subtle, complex and intriguing challenges. This review, taking the PLA(2) enzymes from spitting cobra (Naja nigricollis) venom as examples, describes the mechanism of anticoagulant effects. The strongly anticoagulant CM-IV inhibits both the extrinsic tenase and prothrombinase complexes, whereas the weakly anticoagulant PLA(2) enzymes (CM-I and CM-II) inhibit only the extrinsic tenase complex. CM-IV binds to factor Xa and interferes in its interaction with factor Va and the formation of prothrombinase complex. In contrast, CM-I and CM-II do not affect the formation of prothrombinase complex. In addition, CM-IV inhibits the extrinsic tenase complex by a combination of enzymatic and nonenzymatic mechanisms, while CM-I and CM-II inhibit by only enzymatic mechanism. These functional differences explain the disparity in the anticoagulant potency of N. nigricollis PLA(2) enzymes. Similarly, human secretory enzyme binds to factor Xa and inhibits the prothrombinase complex. We predicted the anticoagulant region of PLA(2) enzymes using a systematic and direct comparison of amino acid sequences. This region between 54 and 77 residues is basic in the strongly anticoagulant PLA(2) enzymes and neutral or negatively charged in weakly and non-anticoagulant enzymes. The prediction is validated independently by us and others using both site directed mutagenesis and synthetic peptides. Thus, strongly anticoagulant CM-IV binds to factor Xa (its target protein) through the specific anticoagulant site on its surface. In contrast, weakly anticoagulant enzymes, which lack the anticoagulant region fail to bind specifically to the target protein, factor Xa in the coagulation cascade. Thus, these studies strongly support the target model which suggests that protein-protein interaction rather than protein-phospholipid interaction determines the pharmacological specificity of PLA(2) enzymes.
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              Prey specificity, comparative lethality and compositional differences of coral snake venoms

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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Rev. Soc. Bras. Med. Trop.
                Sociedade Brasileira de Medicina Tropical - SBMT (Uberaba, MG, Brazil )
                0037-8682
                1678-9849
                June 2017
                : 50
                : 3
                : 365-373
                Affiliations
                [2] Manaus AM orgnameFundação de Medicina Tropical Doutor Heitor Vieira Dourado orgdiv1Centro de Ofidismo da Amazônia Brasil
                [1] Manaus Amazonas orgnameInstituto Nacional de Pesquisas da Amazônia orgdiv1Laboratório de Ecologia e Biotecnologia de Microrganismos da Amazônia Brazil
                Article
                S0037-86822017000300365
                10.1590/0037-8682-0408-2016
                ee2abee1-a712-4630-b1fa-71ccc6016ada

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 25 October 2016
                : 11 April 2017
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 73, Pages: 9
                Product

                SciELO Brazil


                Micrurus surinamensis,Neurotoxins,Phospholipase A2,Biological activities

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